Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Breast cancer

Abstract

Breast cancer is the most frequent malignancy in women worldwide and is curable in ~70–80% of patients with early-stage, non-metastatic disease. Advanced breast cancer with distant organ metastases is considered incurable with currently available therapies. On the molecular level, breast cancer is a heterogeneous disease; molecular features include activation of human epidermal growth factor receptor 2 (HER2, encoded by ERBB2), activation of hormone receptors (oestrogen receptor and progesterone receptor) and/or BRCA mutations. Treatment strategies differ according to molecular subtype. Management of breast cancer is multidisciplinary; it includes locoregional (surgery and radiation therapy) and systemic therapy approaches. Systemic therapies include endocrine therapy for hormone receptor-positive disease, chemotherapy, anti-HER2 therapy for HER2-positive disease, bone stabilizing agents, poly(ADP-ribose) polymerase inhibitors for BRCA mutation carriers and, quite recently, immunotherapy. Future therapeutic concepts in breast cancer aim at individualization of therapy as well as at treatment de-escalation and escalation based on tumour biology and early therapy response. Next to further treatment innovations, equal worldwide access to therapeutic advances remains the global challenge in breast cancer care for the future.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Breast cancer.
Fig. 2: Molecular mutations in breast cancer.
Fig. 3: Immune crosstalk in breast cancer.
Fig. 4: Breast cancer imaging.
Fig. 5: Breast cancer histological types and molecular alterations.
Fig. 6: Algorithm for early breast cancer.
Fig. 7: Breast-conserving surgery.
Fig. 8: Radiation therapy for breast cancer.
Fig. 9: Common metastatic sites in breast cancer.
Fig. 10: Algorithm for advanced breast cancer.
Fig. 11: Emerging targetable pathways in breast cancer.

References

  1. 1.

    Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).

    CAS  Article  Google Scholar 

  2. 2.

    Cardoso, F. et al. European Breast Cancer Conference manifesto on breast centres/units. Eur. J. Cancer 72, 244–250 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  3. 3.

    Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 68, 394–424 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  4. 4.

    Bray, F. et al. Cancer Incidence in Five Continents: inclusion criteria, highlights from Volume X and the global status of cancer registration. Int. J. Cancer 137, 2060–2071 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  5. 5.

    Mariotto, A. B., Etzioni, R., Hurlbert, M., Penberthy, L. & Mayer, M. Estimation of the number of women living with metastatic breast cancer in the United States. Cancer Epidemiol. Biomark. Prev. 26, 809–815 (2017).

    Article  Google Scholar 

  6. 6.

    Ren, J.-X., Gong, Y., Ling, H., Hu, X. & Shao, Z.-M. Racial/ethnic differences in the outcomes of patients with metastatic breast cancer: contributions of demographic, socioeconomic, tumor and metastatic characteristics. Breast Cancer Res. Treat. 173, 225–237 (2019).

    PubMed  Article  PubMed Central  Google Scholar 

  7. 7.

    Torre, L. A., Siegel, R. L., Ward, E. M. & Jemal, A. Global cancer incidence and mortality rates and trends — an update. Cancer Epidemiol. Biomark. Prev. 25, 16–27 (2016).

    Article  Google Scholar 

  8. 8.

    Ginsburg, O. et al. The global burden of women’s cancers: a grand challenge in global health. Lancet 389, 847–860 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  9. 9.

    Allemani, C. et al. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2). Lancet 385, 977–1010 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  10. 10.

    Winters, S., Martin, C., Murphy, D. & Shokar, N. K. Breast cancer epidemiology, prevention, and screening. Prog. Mol. Biol. Transl Sci. 151, 1–32 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  11. 11.

    Hossain, M. S., Ferdous, S. & Karim-Kos, H. E. Breast cancer in South. Asia: a Bangladeshi perspective. Cancer Epidemiol. 38, 465–470 (2014).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    Leong, S. P. L. et al. Is breast cancer the same disease in Asian and western countries? World J. Surg. 34, 2308–2324 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    Bhoo Pathy, N. et al. Breast cancer in a multi-ethnic Asian setting: results from the Singapore–Malaysia hospital-based breast cancer registry. Breast 20, S75–S80 (2011).

    Article  Google Scholar 

  14. 14.

    Raina, V. et al. Clinical features and prognostic factors of early breast cancer at a major cancer center in North India. Indian J. Cancer 42, 40 (2005).

    PubMed  Article  PubMed Central  Google Scholar 

  15. 15.

    Agarwal, G., Pradeep, P. V., Aggarwal, V., Yip, C.-H. & Cheung, P. S. Y. Spectrum of breast cancer in Asian women. World J. Surg. 31, 1031–1040 (2007).

    PubMed  Article  PubMed Central  Google Scholar 

  16. 16.

    Li, C. I., Malone, K. E. & Daling, J. R. Differences in breast cancer hormone receptor status and histology by race and ethnicity among women 50 years of age and older. Cancer Epidemiol. Biomark. Prev. 11, 601–607 (2002).

    Google Scholar 

  17. 17.

    Wong, F. Y., Tham, W. Y., Nei, W. L., Lim, C. & Miao, H. Age exerts a continuous effect in the outcomes of Asian breast cancer patients treated with breast-conserving therapy. Cancer Commun. 38, 39 (2018).

    Article  Google Scholar 

  18. 18.

    Kohler, B. A. et al. Annual report to the nation on the status of cancer, 1975–2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J. Natl Cancer Inst. 107, https://doi.org/10.1093/jnci/djv048 (2015).

  19. 19.

    DeSantis, C. E. et al. Breast cancer statistics, 2015: Convergence of incidence rates between black and white women: Breast Cancer Statistics, 2015. CA Cancer J. Clin. 66, 31–42 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    DeSantis, C. E., Ma, J., Goding Sauer, A., Newman, L. A. & Jemal, A. Breast cancer statistics, 2017, racial disparity in mortality by state: Breast Cancer Statistics, 2017. CA Cancer J. Clin. 67, 439–448 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  21. 21.

    Shiovitz, S. & Korde, L. A. Genetics of breast cancer: a topic in evolution. Ann. Oncol. 26, 1291–1299 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Collaborative Group on Hormonal Factors in Breast Cancer. Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58 209 women with breast cancer and 101 986 women without the disease. Lancet 358, 1389–1399 (2001).

    Article  Google Scholar 

  23. 23.

    Brewer, H. R., Jones, M. E., Schoemaker, M. J., Ashworth, A. & Swerdlow, A. J. Family history and risk of breast cancer: an analysis accounting for family structure. Breast Cancer Res. Treat. 165, 193–200 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  24. 24.

    Huen, M. S. Y., Sy, S. M. H. & Chen, J. BRCA1 and its toolbox for the maintenance of genome integrity. Nat. Rev. Mol. Cell Biol. 11, 138–148 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  25. 25.

    Kuchenbaecker, K. B. et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317, 2402 (2017).

    CAS  Article  Google Scholar 

  26. 26.

    Balmana, J., Diez, O., Rubio, I. T. & Cardoso, F., On behalf of the ESMO Guidelines Working Group. BRCA in breast cancer: ESMO clinical practice guidelines. Ann. Oncol. 22, vi31–vi34 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  27. 27.

    Paluch-Shimon, S. et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO Clinical Practice Guidelines for cancer prevention and screening. Ann. Oncol. 27, v103–v110 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  28. 28.

    Daly, M. B. et al. Genetic/familial high-risk assessment: breast and ovarian, version 2.2015. J. Natl Compr. Cancer Netw. 14, 153–162 (2016).

    Article  Google Scholar 

  29. 29.

    Forbes, C., Fayter, D., de Kock, S. & Quek, R. G. W. A systematic review of international guidelines and recommendations for the genetic screening, diagnosis, GENETIC COUNSELING and treatment of BRCA-mutated breast cancer. Cancer Manag. Res. 2019, 2321–2337 (2019).

    Article  Google Scholar 

  30. 30.

    Robson, M. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 377, 523–533 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  31. 31.

    Litton, J. K. et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N. Engl. J. Med. 379, 753–763 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    FDA. FDA approves olaparib germline BRCA-mutated metastatic breast cancer. Fda.gov https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-olaparib-germline-brca-mutated-metastatic-breast-cancer (2018).

  33. 33.

    FDA. FDA approves talazoparib for gBRCAm HER2-negative locally advanced or metastatic breast cancer. Fda.gov https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-talazoparib-gbrcam-her2-negative-locally-advanced-or-metastatic-breast-cancer (2018).

  34. 34.

    Pasche, B. Recent advances in breast cancer genetics. Cancer Treat. Res. 141, 1–10 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Cobain, E. F., Milliron, K. J. & Merajver, S. D. Updates on breast cancer genetics: clinical implications of detecting syndromes of inherited increased susceptibility to breast cancer. Semin. Oncol. 43, 528–535 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  36. 36.

    Crawford, B. et al. Multi-gene panel testing for hereditary cancer predisposition in unsolved high-risk breast and ovarian cancer patients. Breast Cancer Res. Treat. 163, 383–390 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    Taylor, A. et al. Consensus for genes to be included on cancer panel tests offered by UK genetics services: guidelines of the UK Cancer Genetics Group. J. Med. Genet. 55, 372–377 (2018).

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Althuis, M. D., Dozier, J. M., Anderson, W. F., Devesa, S. S. & Brinton, L. A. Global trends in breast cancer incidence and mortality 1973–1997. Int. J. Epidemiol. 34, 405–412 (2005).

    PubMed  Article  PubMed Central  Google Scholar 

  39. 39.

    Colditz, G. A., Sellers, T. A. & Trapido, E. Epidemiology — identifying the causes and preventability of cancer? Nat. Rev. Cancer 6, 75–83 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  40. 40.

    Britt, K., Ashworth, A. & Smalley, M. Pregnancy and the risk of breast cancer. Endocr. Relat. Cancer 14, 907–933 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    Siwko, S. K. et al. Evidence that an early pregnancy causes a persistent decrease in the number of functional mammary epithelial stem cells — implications for pregnancy-induced protection against breast cancer. Stem Cells 26, 3205–3209 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  42. 42.

    Hilakivi-Clarke, L., de Assis, S. & Warri, A. Exposures to synthetic estrogens at different times during the life, and their effect on breast cancer risk. J. Mammary Gland. Biol. Neoplasia 18, 25–42 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  43. 43.

    Danaei, G., Vander Hoorn, S., Lopez, A. D., Murray, C. J. & Ezzati, M. Causes of cancer in the world: comparative risk assessment of nine behavioural and environmental risk factors. Lancet 366, 1784–1793 (2005).

    PubMed  Article  PubMed Central  Google Scholar 

  44. 44.

    Chen, W. Y., Rosner, B., Hankinson, S. E., Colditz, G. A. & Willett, W. C. Moderate alcohol consumption during adult life, drinking patterns, and breast cancer risk. JAMA 306, 1884 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. 45.

    Singletary, K. W. & Gapstur, S. M. Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms. JAMA 286, 2143 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  46. 46.

    Smith-Warner, S. A. et al. Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 279, 535 (1998).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  47. 47.

    Bandera, E. V., Maskarinec, G., Romieu, I. & John, E. M. Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective. Adv. Nutr. 6, 803–819 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Picon-Ruiz, M., Morata-Tarifa, C., Valle-Goffin, J. J., Friedman, E. R. & Slingerland, J. M. Obesity and adverse breast cancer risk and outcome: mechanistic insights and strategies for intervention: breast cancer, inflammation, and obesity. CA Cancer J. Clin. 67, 378–397 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Shieh, Y. et al. Body mass index, mammographic density, and breast cancer risk by estrogen receptor subtype. Breast Cancer Res. 21, 48 (2019).

    PubMed  PubMed Central  Article  Google Scholar 

  50. 50.

    Suzuki, Y., Tsunoda, H., Kimura, T. & Yamauchi, H. BMI change and abdominal circumference are risk factors for breast cancer, even in Asian women. Breast Cancer Res. Treat. 166, 919–925 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  51. 51.

    Del Pup, L., Codacci-Pisanelli, G. & Peccatori, F. Breast cancer risk of hormonal contraception: counselling considering new evidence. Crit. Rev. Oncol. Hematol. 137, 123–130 (2019).

    PubMed  Article  PubMed Central  Google Scholar 

  52. 52.

    Busund, M. et al. Progestin-only and combined oral contraceptives and receptor-defined premenopausal breast cancer risk: the Norwegian Women and Cancer Study. Int. J. Cancer 142, 2293–2302 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. 53.

    Mørch, L. S. et al. Contemporary hormonal contraception and the risk of breast cancer. N. Engl. J. Med. 377, 2228–2239 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  54. 54.

    Ganz, P. A. et al. Supportive care after curative treatment for breast cancer (survivorship care): resource allocations in low- and middle-income countries. A Breast Health Global Initiative 2013 consensus statement. Breast 22, 606–615 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  55. 55.

    Burris, J. L., Armeson, K. & Sterba, K. R. A closer look at unmet needs at the end of primary treatment for breast cancer: a longitudinal pilot study. Behav. Med. 41, 69–76 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  56. 56.

    Coughlin, S. S., Yoo, W., Whitehead, M. S. & Smith, S. A. Advancing breast cancer survivorship among African-American women. Breast Cancer Res. Treat. 153, 253–261 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  57. 57.

    Bodai, B. Breast cancer survivorship: a comprehensive review of long-term medical issues and lifestyle recommendations. Perm. J. 19, 48–79 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  58. 58.

    Ho, P. J., Gernaat, S. A. M., Hartman, M. & Verkooijen, H. M. Health-related quality of life in Asian patients with breast cancer: a systematic review. BMJ Open 8, e020512 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  59. 59.

    Miyashita, M. et al. Unmet information needs and quality of life in young breast cancer survivors in japan. Cancer Nurs. 38, E1–E11 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  60. 60.

    Bombonati, A. & Sgroi, D. C. The molecular pathology of breast cancer progression. J. Pathol. 223, 307–317 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  61. 61.

    Ellis, M. J. et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 486, 353–360 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  62. 62.

    Lopez-Garcia, M. A., Geyer, F. C., Lacroix-Triki, M., Marchió, C. & Reis-Filho, J. S. Breast cancer precursors revisited: molecular features and progression pathways: molecular evolution of breast cancer. Histopathology 57, 171–192 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  63. 63.

    Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47–54 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  64. 64.

    Yates, L. R. & Desmedt, C. Translational genomics: practical applications of the genomic revolution in breast cancer. Clin. Cancer Res. 23, 2630–2639 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  65. 65.

    Heitzer, E., Haque, I. S., Roberts, C. E. S. & Speicher, M. R. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat. Rev. Genet. 20, 71–88 (2019).

    CAS  Article  Google Scholar 

  66. 66.

    Ediriweera, M. K., Tennekoon, K. H. & Samarakoon, S. R. Emerging role of histone deacetylase inhibitors as anti-breast-cancer agents. Drug Discov. Today 24, 685–702 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  67. 67.

    Munster, P. N. et al. A phase II study of the histone deacetylase inhibitor vorinostat combined with tamoxifen for the treatment of patients with hormone therapy-resistant breast cancer. Br. J. Cancer 104, 1828–1835 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  68. 68.

    Zhou, Y., Wang, Y., Zhang, K., Zhu, J. & Ning, Z. Reverse effect of chidamide on endocrine resistance in estrogen receptor-positive breast cancer. J. Shenzhen Univ. Sci. Eng. 35, 339 (2018).

    Article  Google Scholar 

  69. 69.

    Jiang, Z. et al. Phase III trial of chidamide, a subtype-selective histone deacetylase (HDAC) inhibitor, in combination with exemestane in patients with hormone receptor-positive advanced breast cancer [abstract]. Ann. Oncol. 29, 283O_PR (2018).

    Article  Google Scholar 

  70. 70.

    Williams, C. & Lin, C.-Y. Oestrogen receptors in breast cancer: basic mechanisms and clinical implications. Ecancermedicalscience 7, 370 (2013).

    PubMed  PubMed Central  Google Scholar 

  71. 71.

    Levin, E. R. & Pietras, R. J. Estrogen receptors outside the nucleus in breast cancer. Breast Cancer Res. Treat. 108, 351–361 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  72. 72.

    Santen, R. J. Clinical review: effect of endocrine therapies on bone in breast cancer patients. J. Clin. Endocrinol. Metab. 96, 308–319 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  73. 73.

    Ruffell, B. et al. Leukocyte composition of human breast cancer. Proc. Natl Acad. Sci. USA 109, 2796–2801 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  74. 74.

    Solinas, C., Carbognin, L., De Silva, P., Criscitiello, C. & Lambertini, M. Tumor-infiltrating lymphocytes in breast cancer according to tumor subtype: current state of the art. Breast 35, 142–150 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  75. 75.

    Nagarajan, D. & McArdle, S. Immune landscape of breast cancers. Biomedicines 6, 20 (2018).

    PubMed Central  Article  CAS  Google Scholar 

  76. 76.

    Savas, P. et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat. Rev. Clin. Oncol. 13, 228–241 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  77. 77.

    Dieci, M. V. et al. Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: a report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. Semin. Cancer Biol. 52, 16–25 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  78. 78.

    Boudreau, A., van’t Veer, L. J. & Bissell, M. J. An ‘elite hacker’: breast tumors exploit the normal microenvironment program to instruct their progression and biological diversity. Cell Adhes. Migr. 6, 236–248 (2012).

    Article  Google Scholar 

  79. 79.

    Smyth, M. J., Dunn, G. P. & Schreiber, R. D. Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv. Immunol. 90, 1–50 (2006).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  80. 80.

    Schreiber, R. D., Old, L. J. & Smyth, M. J. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science 331, 1565–1570 (2011).

    CAS  Article  Google Scholar 

  81. 81.

    Buonomo, O. C. et al. New insights into the metastatic behavior after breast cancer surgery, according to well-established clinicopathological variables and molecular subtypes. PLOS ONE 12, e0184680 (2017).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  82. 82.

    Gobbini, E. et al. Time trends of overall survival among metastatic breast cancer patients in the real-life ESME cohort. Eur. J. Cancer 96, 17–24 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  83. 83.

    Santé Publique France. Breast cancer [French]. Santepubliquefrance.fr https://www.santepubliquefrance.fr/maladies-et-traumatismes/cancers/cancer-du-sein (2019).

  84. 84.

    Zhang, K. et al. Clinical value of circulating ESR1 mutations for patients with metastatic breast cancer: a meta-analysis. Cancer Manag. Res. 10, 2573–2580 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  85. 85.

    Yates, L. R. et al. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell 32, 169–184.e7 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  86. 86.

    Gingras, I., Salgado, R. & Ignatiadis, M. Liquid biopsy: will it be the ‘magic tool’ for monitoring response of solid tumors to anticancer therapies? Curr. Opin. Oncol. 27, 560–567 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  87. 87.

    Aurilio, G. et al. A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur. J. Cancer 50, 277–289 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  88. 88.

    Independent, U. K. Panel on breast cancer screening. the benefits and harms of breast cancer screening: an independent review. Lancet 380, 1778–1786 (2012).

    Article  Google Scholar 

  89. 89.

    Nelson, H. D. et al. Effectiveness of breast cancer screening: systematic review and meta-analysis to update the 2009 U.S. Preventive Services Task Force recommendation. Ann. Intern. Med. 164, 244–255 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  90. 90.

    Lauby-Secretan, B. et al. Breast-cancer screening — viewpoint of the IARC Working Group. N. Engl. J. Med. 372, 2353–2358 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  91. 91.

    Houssami, N. Overdiagnosis of breast cancer in population screening: does it make breast screening worthless? Cancer Biol. Med. 14, 1–8 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  92. 92.

    Suhrke, P. et al. Effect of mammography screening on surgical treatment for breast cancer in Norway: comparative analysis of cancer registry data. BMJ 343, d4692–d4692 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  93. 93.

    Stang, A., Kääb-Sanyal, V., Hense, H.-W., Becker, N. & Kuss, O. Effect of mammography screening on surgical treatment for breast cancer: a nationwide analysis of hospitalization rates in Germany 2005–2009. Eur. J. Epidemiol. 28, 689–696 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  94. 94.

    IARC Handbooks of Cancer Prevention. Breast Cancer Screening (Volume 15). Iarc.fr http://publications.iarc.fr/Book-And-Report-Series/Iarc-Handbooks-Of-Cancer-Prevention/Breast-Cancer-Screening-2016 (2016).

  95. 95.

    Nelson, H. D. et al. Harms of breast cancer screening: systematic review to update the 2009 U.S. Preventive Services Task Force recommendation. Ann. Intern. Med. 164, 256–267 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  96. 96.

    Carter, J. L., Coletti, R. J. & Harris, R. P. Quantifying and monitoring overdiagnosis in cancer screening: a systematic review of methods. BMJ 350, g7773 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  97. 97.

    Saslow, D. et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J. Clin. 57, 75–89 (2007).

    PubMed  Article  PubMed Central  Google Scholar 

  98. 98.

    Phi, X.-A. et al. Magnetic resonance imaging improves breast screening sensitivity in BRCA mutation carriers age ≥ 50 years: evidence from an individual patient data meta-analysis. J. Clin. Oncol. 33, 349–356 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  99. 99.

    Sardanelli, F. et al. Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. Eur. J. Cancer 46, 1296–1316 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  100. 100.

    Melnikow, J. et al. Supplemental screening for breast cancer in women with dense breasts: a systematic review for the U.S. preventive services task force. Ann. Intern. Med. 164, 268–278 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  101. 101.

    Houssami, N. & Lee, C. I. The impact of legislation mandating breast density notification — review of the evidence. Breast 42, 102–112 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  102. 102.

    Marinovich, M. L., Hunter, K. E., Macaskill, P. & Houssami, N. Breast cancer screening using tomosynthesis or mammography: a meta-analysis of cancer detection and recall. J. Natl Cancer Inst. 110, 942–949 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  103. 103.

    Irwig, L., Macaskill, P. & Houssami, N. Evidence relevant to the investigation of breast symptoms: the triple test. Breast 11, 215–220 (2002).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  104. 104.

    Houssami, N., Ciatto, S., Turner, R. M., Cody, H. S. & Macaskill, P. Preoperative ultrasound-guided needle biopsy of axillary nodes in invasive breast cancer: meta-analysis of its accuracy and utility in staging the axilla. Ann. Surg. 254, 243–251 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  105. 105.

    Morrow, M., Waters, J. & Morris, E. MRI for breast cancer screening, diagnosis, and treatment. Lancet 378, 1804–1811 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  106. 106.

    Srigley, J. R. et al. Standardized synoptic cancer pathology reporting: a population-based approach. J. Surg. Oncol. 99, 517–524 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  107. 107.

    World Heath Organisation. WHO Classification of Tumours of the Breast, Fourth Edition. (World Health Organization, 2012).

  108. 108.

    Elston, C. W. & Ellis, I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19, 403–410 (1991).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  109. 109.

    National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Nccn.org https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf (2018).

  110. 110.

    Curigliano, G. et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann. Oncol. 28, 1700–1712 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  111. 111.

    Senkus, E. et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 24 (Suppl. 6), vi7-vi23 (2013).

    PubMed  PubMed Central  Google Scholar 

  112. 112.

    Hammond, M. E. H. et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J. Clin. Oncol. 28, 2784–2795 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  113. 113.

    Wolff, A. C. et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline focused update. J. Clin. Oncol. 36, 2105–2122 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  114. 114.

    Dowsett, M. et al. Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J. Natl Cancer Inst. 103, 1656–1664 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  115. 115.

    Rakha, E. A. et al. The prognostic significance of lymphovascular invasion in invasive breast carcinoma. Cancer 118, 3670–3680 (2012).

    PubMed  Article  PubMed Central  Google Scholar 

  116. 116.

    Barrio, A. V. & Morrow, M. Appropriate margin for lumpectomy excision of invasive breast cancer. Chin. Clin. Oncol. 5, 35–35 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  117. 117.

    Chung, A. et al. Impact of consensus guidelines by the Society of Surgical Oncology and the American Society for Radiation Oncology on margins for breast-conserving surgery in stages 1 and 2 invasive breast cancer. Ann. Surg. Oncol. 22, 422–427 (2015).

    Article  Google Scholar 

  118. 118.

    Schulman, A. M. et al. Reexcision surgery for breast cancer: an analysis of the American Society of Breast Surgeons (ASBrS) MasterySM database following the SSO-ASTRO “no ink on tumor” guidelines. Ann. Surg. Oncol. 24, 52–58 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  119. 119.

    Morrow, M. et al. Society of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. Pract. Radiat. Oncol. 6, 287–295 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  120. 120.

    Morrow, M. et al. Society of Surgical Oncology–American Society for Radiation Oncology–American Society of Clinical Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. J. Clin. Oncol. 34, 4040–4046 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  121. 121.

    Moran, M. S. et al. Society of Surgical Oncology–American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Int. J. Radiat. Oncol. Biol. Phys. 88, 553–564 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  122. 122.

    Amin, M. B. et al. The Eighth Edition AJCC Cancer Staging Manual: continuing to build a bridge from a population-based to a more ‘personalized’ approach to cancer staging. CA Cancer J. Clin. 67, 93–99 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  123. 123.

    Tao, L. et al. Breast cancer mortality in older and younger breast cancer patients in California. Cancer Epidemiol. Biomark. Prev. 28, 303–310 (2018).

    Article  Google Scholar 

  124. 124.

    Salgado, R. et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann. Oncol. 26, 259–271 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  125. 125.

    Green, A. R. et al. Nottingham Prognostic Index Plus: validation of a clinical decision making tool in breast cancer in an independent series. J. Pathol. Clin. Res. 2, 32–40 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  126. 126.

    Candido dos Reis, F. J. et al. An updated PREDICT breast cancer prognostication and treatment benefit prediction model with independent validation. Breast Cancer Res. 19, 58 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  127. 127.

    Phung, M. T., Tin Tin, S. & Elwood, J. M. Prognostic models for breast cancer: a systematic review. BMC Cancer 19, 230 (2019).

    PubMed  PubMed Central  Article  Google Scholar 

  128. 128.

    Senkus, E. et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 26 (Suppl. 5), v8-v30 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  129. 129.

    Cortazar, P. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384, 164–172 (2014).

    Article  Google Scholar 

  130. 130.

    Cardoso, F. et al. 70-Gene signature as an aid to treatment decisions in early-stage breast cancer. N. Engl. J. Med. 375, 717–729 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  131. 131.

    Sparano, J. A. et al. Prospective validation of a 21-gene expression assay in breast cancer. N. Engl. J. Med. 373, 2005–2014 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  132. 132.

    Sparano, J. A. et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N. Engl. J. Med. 379, 111–121 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  133. 133.

    Harris, L. N. et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline. J. Clin. Oncol. 34, 1134–1150 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  134. 134.

    Krop, I. et al. Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J. Clin. Oncol. 35, 2838–2847 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  135. 135.

    Nitz, U. et al. West German Study PlanB trial: adjuvant four cycles of epirubicin and cyclophosphamide plus docetaxel versus six cycles of docetaxel and cyclophosphamide in HER2-negative early breast cancer. J. Clin. Oncol. 37, 799–808 (2019).

    CAS  PubMed  Article  Google Scholar 

  136. 136.

    Sestak, I. Risk stratification in early breast cancer in premenopausal and postmenopausal women: integrating genomic assays with clinicopathological features. Curr. Opin. Oncol. 1, 29–34 (2018).

    Article  Google Scholar 

  137. 137.

    McLaughlin, S. A. Surgical management of the breast: breast conservation therapy and mastectomy. Surg. Clin. North Am. 93, 411–428 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  138. 138.

    Margenthaler, J. A. & Ollila, D. W. Breast conservation therapy versus mastectomy: shared decision-making strategies and overcoming decisional conflicts in your patients. Ann. Surg. Oncol. 23, 3133–3137 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  139. 139.

    Buchholz, T. A., Mittendorf, E. A. & Hunt, K. K. Surgical considerations after neoadjuvant chemotherapy: breast conservation therapy. J. Natl Cancer Inst. Monogr. 2015, 11–14 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  140. 140.

    Houssami, N., Macaskill, P., Luke Marinovich, M. & Morrow, M. The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis. Ann. Surg. Oncol. 21, 717–730 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  141. 141.

    Morrow, M., Harris, J. R. & Schnitt, S. J. Surgical margins in lumpectomy for breast cancer — bigger is not better. N. Engl. J. Med. 367, 79–82 (2012). This commentary and the meta-analysis by Houssami et al. (2014) settled the decade-long discussions about surgical resection margins and are, therefore, landmark contributions.

    PubMed  Article  PubMed Central  Google Scholar 

  142. 142.

    Tan, M. P., Sitoh, N. Y. & Sim, A. S. The value of intraoperative frozen section analysis for margin status in breast conservation surgery in a nontertiary institution. Int. J. Breast Cancer https://doi.org/10.1155/2014/715404 (2014).

    Article  Google Scholar 

  143. 143.

    Boughey, J. C. et al. Impact of analysis of frozen-section margin on reoperation rates in women undergoing lumpectomy for breast cancer: evaluation of the National Surgical Quality Improvement Program data. Surgery 156, 190–197 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  144. 144.

    Haloua, M. H. et al. A systematic review of oncoplastic breast-conserving surgery: current weaknesses and future prospects. Ann. Surg. 257, 609–620 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  145. 145.

    Benelli, L. A new periareolar mammaplasty: the ‘round block’ technique. Aesthetic Plast. Surg. 14, 93–100 (1990).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  146. 146.

    Clough, K. B., Kaufman, G. J., Nos, C., Buccimazza, I. & Sarfati, I. M. Improving breast cancer surgery: a classification and quadrant per quadrant atlas for oncoplastic surgery. Ann. Surg. Oncol. 17, 1375–1391 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  147. 147.

    Yao, K., Winchester, D. J., Czechura, T. & Huo, D. Contralateral prophylactic mastectomy and survival: report from the national cancer data base, 1998–2002. Breast Cancer Res. Treat. 142, 465–476 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  148. 148.

    Vila, J., Gandini, S. & Gentilini, O. Overall survival according to type of surgery in young (≤40 years) early breast cancer patients: a systematic meta-analysis comparing breast-conserving surgery versus mastectomy. Breast 24, 175–181 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  149. 149.

    Lucci, A. et al. Surgical complications associated with sentinel lymph node dissection (SLND) plus axillary lymph node dissection compared with SLND alone in the American College of Surgeons Oncology Group trial Z0011. J. Clin. Oncol. 25, 3657–3663 (2007).

    PubMed  Article  PubMed Central  Google Scholar 

  150. 150.

    Krag, D. N. et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 11, 927–933 (2010). This large clinical trial confirms that there is no overall survival difference between sentinel lymph node biopsy and axillary lymph node dissection.

    PubMed  PubMed Central  Article  Google Scholar 

  151. 151.

    Veronesi, U. et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N. Engl. J. Med. 349, 546–553 (2003).

    PubMed  Article  PubMed Central  Google Scholar 

  152. 152.

    Giuliano, A. E. et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann. Surg. 264, 413–420 (2016).

    PubMed  PubMed Central  Article  Google Scholar 

  153. 153.

    Balic, M., Thomssen, C., Würstlein, R., Gnant, M. & Harbeck, N. St. Gallen/Vienna 2019: a brief summary of the consensus discussion on the optimal primary breast cancer treatment. Breast Care 14, 1–8 (2019).

  154. 154.

    Kaidar-Person, O., Meattini, I. & Poortmans, P. M. P. Between uncertainties and overtreatment. Int. J. Radiat. Oncol. 104, 15–16 (2019).

    Article  Google Scholar 

  155. 155.

    Kuehn, T. et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol. 14, 609–618 (2013).

    Article  Google Scholar 

  156. 156.

    King, T. A. & Morrow, M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat. Rev. Clin. Oncol. 12, 335–343 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  157. 157.

    Giuliano, A. E. et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 305, 569–575 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  158. 158.

    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378, 1707–1716 (2011). This meta-analysis underlines that the contribution of radiation therapy should always be the standard approach for breast-conserving therapy.

    Article  CAS  Google Scholar 

  159. 159.

    EBCTCG (Early Breast Cancer Trialists’ Collaborative Group). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet 383, 2127–2135 (2014). This meta-analysis helps us to better identify those patients who would benefit most from radiation therapy after mastectomy.

    Article  Google Scholar 

  160. 160.

    Jatoi, I., Benson, J. R. & Kunkler, I. Hypothesis: can the abscopal effect explain the impact of adjuvant radiotherapy on breast cancer mortality? NPJ Breast Cancer 4, 8 (2018).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  161. 161.

    Bartelink, H. et al. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol. 16, 47–56 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  162. 162.

    Poortmans, P. Postmastectomy radiation in breast cancer with one to three involved lymph nodes: ending the debate. Lancet 383, 2104–2106 (2014).

    Article  Google Scholar 

  163. 163.

    Poortmans, P. M. et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N. Engl. J. Med. 373, 317–327 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  164. 164.

    Whelan, T. J. et al. Regional nodal irradiation in early-stage breast cancer. N. Engl. J. Med. 373, 307–316 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  165. 165.

    Thorsen, L. B. J. et al. DBCG-IMN: a population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J. Clin. Oncol. 34, 314–320 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  166. 166.

    Curigliano, G. et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann. Oncol. 29, 2153–2153 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  167. 167.

    Oliai, C. & Hurvitz, S. A. The debate over post-mastectomy radiotherapy should continue: breast cancer. Nat. Rev. Clin. Oncol. 12, 567–568 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  168. 168.

    Recht, A. et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. Ann. Surg. Oncol. 24, 38–51 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  169. 169.

    Dodwell, D. et al. Abstract GS4-02: regional lymph node irradiation in early stage breast cancer: an EBCTCG meta-analysis of 13,000 women in 14 trials. in General Session Abstracts GS4-02-GS4-02 https://doi.org/10.1158/1538-7445.SABCS18-GS4-02 (American Association for Cancer Research, 2019).

  170. 170.

    Kunkler, I. H., Canney, P., van Tienhoven, G. & Russell, N. S. MRC/EORTC (BIG 2-04) SUPREMO Trial Management Group. Elucidating the role of chest wall irradiation in ‘intermediate-risk’. breast cancer: The MRC/EORTC SUPREMO trial. Clin. Oncol. R. Coll. Radiol. 20, 31–34 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  171. 171.

    Poortmans, P., Aznar, M. & Bartelink, H. Quality indicators for breast cancer: revisiting historical evidence in the context of technology changes. Semin. Radiat. Oncol. 22, 29–39 (2012).

    PubMed  Article  PubMed Central  Google Scholar 

  172. 172.

    Osman, S. O. S., Hol, S., Poortmans, P. M. & Essers, M. Volumetric modulated arc therapy and breath-hold in image-guided locoregional left-sided breast irradiation. Radiother. Oncol. 112, 17–22 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  173. 173.

    Essers, M., Poortmans, P. M., Verschueren, K., Hol, S. & Cobben, D. C. P. Should breathing adapted radiotherapy also be applied for right-sided breast irradiation? Acta Oncol. 55, 460–465 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  174. 174.

    Poortmans, P. M. P., Arenas, M. & Livi, L. Over-irradiation. Breast 31, 295–302 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  175. 175.

    Blamey, R. W. et al. Radiotherapy or tamoxifen after conserving surgery for breast cancers of excellent prognosis: British Association of Surgical Oncology (BASO) II trial. Eur. J. Cancer 49, 2294–2302 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  176. 176.

    McGuire, S. E. et al. Postmastectomy radiation improves the outcome of patients with locally advanced breast cancer who achieve a pathologic complete response to neoadjuvant chemotherapy. Int. J. Radiat. Oncol. Biol. Phys. 68, 1004–1009 (2007).

    PubMed  PubMed Central  Article  Google Scholar 

  177. 177.

    Mamounas, E. P. et al. Predictors of locoregional recurrence after neoadjuvant chemotherapy: results from combined analysis of national surgical adjuvant breast and bowel project B-18 and B-27. J. Clin. Oncol. 30, 3960–3966 (2012).

    PubMed  PubMed Central  Article  Google Scholar 

  178. 178.

    Krug, D. et al. Individualization of post-mastectomy radiotherapy and regional nodal irradiation based on treatment response after neoadjuvant chemotherapy for breast cancer: a systematic review. Strahlenther. Onkol. 194, 607–618 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  179. 179.

    Amoroso, V. et al. International Expert Consensus on Primary Systemic Therapy in the Management of Early Breast Cancer: Highlights of the Fifth Symposium on Primary Systemic Therapy in the Management of Operable Breast Cancer, Cremona, Italy (2013). J. Natl Cancer Inst. Monogr. 2015, 90–96 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  180. 180.

    Offersen, B. V. et al. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer, version 1.1. Radiother. Oncol. 118, 205–208 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  181. 181.

    Haviland, J. S. et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 14, 1086–1094 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  182. 182.

    Whelan, T. J. et al. Long-term results of hypofractionated radiation therapy for breast cancer. N. Engl. J. Med. 362, 513–520 (2010).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  183. 183.

    Wang, S.-L. et al. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 20, 352–360 (2019).

    PubMed  Article  PubMed Central  Google Scholar 

  184. 184.

    Brouwers, P. J. A. M. et al. Predictors for poor cosmetic outcome in patients with early stage breast cancer treated with breast conserving therapy: results of the Young Boost trial. Radiother. Oncol. 128, 434–441 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  185. 185.

    Polgár, C. et al. Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: recommendations of the groupe européen de curiethérapie-european society for therapeutic radiology and oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009). Radiother. Oncol. 94, 264–273 (2010).

    PubMed  Article  PubMed Central  Google Scholar 

  186. 186.

    Correa, C. et al. Accelerated partial breast irradiation: executive summary for the update of an ASTRO Evidence-Based. Consensus Statement. Pract. Radiat. Oncol. 7, 73–79 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  187. 187.

    Miranda, F. A. et al. Accelerated partial breast irradiation: current status with a focus on clinical practice. Breast J. https://doi.org/10.1111/tbj.13164 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  188. 188.

    Marta, G. N. et al. Effectiveness of different accelerated partial breast irradiation techniques for the treatment of breast cancer patients: systematic review using indirect comparisons of randomized clinical trials. Rep. Pract. Oncol. Radiother. 24, 165–174 (2019).

    PubMed  Article  PubMed Central  Google Scholar 

  189. 189.

    Veronesi, U. et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 14, 1269–1277 (2013).

    PubMed  Article  PubMed Central  Google Scholar 

  190. 190.

    Vaidya, J. S. et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial. Lancet 383, 603–613 (2014).

    Article  Google Scholar 

  191. 191.

    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378, 771–784 (2011).

    Article  CAS  Google Scholar 

  192. 192.

    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomized trials. Lancet 379, 432–444 (2012). This meta-analysis demonstrates the benefits of adjuvant chemotherapy in early breast cancer.

  193. 193.

    Rastogi, P. et al. Preoperative chemotherapy: updates of national surgical adjuvant breast and bowel project protocols B-18 and B-27. J. Clin. Oncol. 26, 778–785 (2008).

    PubMed  Article  PubMed Central  Google Scholar 

  194. 194.

    Francis, P. A. et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N. Engl. J. Med. 379, 122–137 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  195. 195.

    Gnant, M. et al. Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12. Ann. Oncol. 26, 313–320 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  196. 196.

    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet 386, 1341–1352 (2015). This meta-analysis demonstrates the benefit of the two individual options for adjuvant endocrine therapy in postmenopausal patients with early breast cancer.

    Article  CAS  Google Scholar 

  197. 197.

    Pan, H. et al. 20-Year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N. Engl. J. Med. 377, 1836–1846 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  198. 198.

    Gray, R. et al. Increasing the dose density of adjuvant chemotherapy by shortening intervals between courses or by sequential drug administration significantly reduces both disease recurrence and breast cancer mortality: an EBCTCG meta-analysis of 21,000 women in 16 randomised trials [abstract]. SABCS GS1-GS01 (2018).

  199. 199.

    Finn, R. S. et al. Palbociclib and letrozole in advanced breast cancer. N. Engl. J. Med. 375, 1925–1936 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  200. 200.

    Hortobagyi, G. N. et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N. Engl. J. Med. 375, 1738–1748 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  201. 201.

    Goetz, M. P. et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J. Clin. Oncol. 35, 3638–3646 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  202. 202.

    Mackey, J. R. et al. Long-term outcomes after adjuvant treatment of sequential versus combination docetaxel with doxorubicin and cyclophosphamide in node-positive breast cancer: BCIRG-005 randomized trial. Ann. Oncol. 27, 1041–1047 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  203. 203.

    Del Mastro, L. et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2×2 factorial, randomised phase 3 trial. Lancet 385, 1863–1872 (2015).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  204. 204.

    Blum, J. L. et al. Anthracyclines in early breast cancer: the ABC Trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J. Clin. Oncol. 35, 2647–2655 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  205. 205.

    Gray, R. et al. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet 393, 1440–1452 (2019).

    Article  Google Scholar 

  206. 206.

    Gianni, L. et al. 5-Year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 17, 791–800 (2016).

    CAS  Article  Google Scholar 

  207. 207.

    von Minckwitz, G. et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N. Engl. J. Med. 380, 617–628 (2018).

    Article  Google Scholar 

  208. 208.

    von Minckwitz, G. et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N. Engl. J. Med. 377, 122–131 (2017).

    Article  Google Scholar 

  209. 209.

    Martin, M. et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 18, 1688–1700 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  210. 210.

    Tolaney, S. M. et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N. Engl. J. Med. 372, 134–141 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  211. 211.

    Tolaney, S. M. et al. Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC). J. Clin. Oncol. 35, 511–511 (2017).

    Article  Google Scholar 

  212. 212.

    Earl, H. M. et al. 6 versus 12 months of adjuvant trastuzumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-free survival results of a randomised phase 3 non-inferiority trial. Lancet 393, 2599–2612 (2019).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  213. 213.

    Pivot, X. et al. Either 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 14, 741–748 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  214. 214.

    Joensuu, H. et al. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2–positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 4, 1199 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  215. 215.

    Piccart-Gebhart, M. J. et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 353, 1659–1672 (2005).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  216. 216.

    Goldhirsch, A. et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet 382, 1021–1028 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  217. 217.

    Hahnen, E. et al. Germline mutation status, pathological complete response, and disease-free survival in triple-negative breast cancer: secondary analysis of the GeparSixto randomized clinical trial. JAMA Oncol. 3, 1378–1385 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  218. 218.

    Sikov, W. M. et al. Impact of the addition of carboplatin and/or bevacizumab to neoadjuvant once-per-week paclitaxel followed by dose-dense doxorubicin and cyclophosphamide on pathologic complete response rates in stage II to III triple-negative breast cancer: CALGB 40603 (Alliance). J. Clin. Oncol. 33, 13–21 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  219. 219.

    Masuda, N. et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N. Engl. J. Med. 376, 2147–2159 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  220. 220.

    Gnant, M. et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 386, 433–443 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  221. 221.

    Gnant, M. et al. Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 20, 339–351 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  222. 222.

    Coleman, R. E. et al. Adjuvant denosumab in early breast cancer: first results from the international multicenter randomized phase III placebo controlled D-CARE study [abstract]. J. Clin. Oncol. 36 (Suppl.), a501 (2018).

    Article  Google Scholar 

  223. 223.

    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet 386, 1353–1361 (2015).

    Article  CAS  Google Scholar 

  224. 224.

    Coleman, R. E. et al. Benefits and risks of adjuvant treatment with zoledronic acid in stage II/III breast cancer. 10 years follow-up of the AZURE randomized clinical trial (BIG 01/04). J. Bone Oncol. 13, 123–135 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  225. 225.

    Cardoso, F. et al. 4th ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 4)†. Ann. Oncol. 29, 1634–1657 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  226. 226.

    Golse, N. & Adam, R. Liver metastases from breast cancer: what role for surgery? Indications and results. Clin. Breast Cancer 17, 256–265 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  227. 227.

    Xie, Y. et al. Surgery of the primary tumor improves survival in women with stage IV breast cancer in southwest China: a retrospective analysis. Medicine 96, e7048 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  228. 228.

    Shien, T. & Doihara, H. Resection of the primary tumor in stage IV breast cancer. World J. Clin. Oncol. 5, 82–85 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  229. 229.

    Badwe, R. et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol. 16, 1380–1388 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  230. 230.

    Soran, A., Ozbas, S., Kelsey, S. F. & Gulluoglu, B. M. Randomized trial comparing locoregional resection of primary tumor with no surgery in stage IV breast cancer at the presentation (Protocol MF07-01): a study of Turkish Federation of the National Societies for Breast Diseases. Breast J. 15, 399–403 (2009).

    PubMed  Article  PubMed Central  Google Scholar 

  231. 231.

    Fitzal, F. et al. Impact of breast surgery in primary metastasized breast cancer: outcomes of the prospective randomized phase III ABCSG-28 POSYTIVE Trial. Ann. Surg. https://doi.org/10.1097/SLA.0000000000002771 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  232. 232.

    Barinoff, J. et al. Primary metastatic breast cancer in the era of targeted therapy — prognostic impact and the role of breast tumour surgery. Eur. J. Cancer 83, 116–124 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  233. 233.

    Shien, T. et al. A randomized controlled trial comparing primary tumor resection plus systemic therapy with systemic therapy alone in metastatic breast cancer (JCOG1017 PRIM-BC). J. Clin. Oncol. 35, TPS588–TPS588 (2017).

    Article  Google Scholar 

  234. 234.

    Cameron, D. Removing the primary tumour in metastatic breast cancer. Lancet Oncol. 16, 1284–1285 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  235. 235.

    Dare, A. J. et al. Surgical Services for Cancer Care. in Cancer: Disease Control Priorities, Third Edition (Volume 3) (eds. Gelband, H., Jha, P., Sankaranarayanan, R. & Horton, S.) (The International Bank for Reconstruction and Development/The World Bank, 2015).

  236. 236.

    Phillips, C., Jeffree, R. & Khasraw, M. Management of breast cancer brain metastases: a practical review. Breast 31, 90–98 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  237. 237.

    Thavarajah, N. et al. Continued success in providing timely palliative radiation therapy at the rapid response radiotherapy program: a review of 2008–2012. Curr. Oncol. 20, e206–e211 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  238. 238.

    Chow, E. et al. Single versus multiple fractions of repeat radiation for painful bone metastases: a randomised, controlled, non-inferiority trial. Lancet Oncol. 15, 164–171 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  239. 239.

    Sologuren, I., Rodríguez-Gallego, C. & Lara, P. C. Immune effects of high dose radiation treatment: implications of ionizing radiation on the development of bystander and abscopal effects. Transl Cancer Res. 3, 18-31–31 (2014).

    Google Scholar 

  240. 240.

    Morgan, S. C. & Parker, C. C. Local treatment of metastatic cancer — killing the seed or disturbing the soil? Nat. Rev. Clin. Oncol. 8, 504–506 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  241. 241.

    Morgan, S., Caudrelier, J.-M. & Clemons, M. Radiotherapy to the primary tumor is associated with improved survival in stage IV breast cancer [abstract]. SABCS P4, 16–06 (2012).

    Google Scholar 

  242. 242.

    Bernier, J. Immuno-oncology: allying forces of radio- and immuno-therapy to enhance cancer cell killing. Crit. Rev. Oncol. Hematol. 108, 97–108 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  243. 243.

    Fietz, T. et al. Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer — rResults from the prospective German TMK cohort study. Breast. 34, 122–130 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  244. 244.

    Rugo, H. S. et al. Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline. J. Clin. Oncol. 34, 3069–3103 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  245. 245.

    Turner, N. C. et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N. Engl. J. Med. 379, 1926–1936 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  246. 246.

    Miles, D. W. et al. First-line bevacizumab in combination with chemotherapy for HER2-negative metastatic breast cancer: pooled and subgroup analyses of data from 2447 patients. Ann. Oncol. 24, 2773–2780 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  247. 247.

    Giordano, S. H. et al. Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: American Society of Clinical Oncology clinical practice guideline. J. Clin. Oncol. 32, 2078–2099 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  248. 248.

    Partridge, A. H. et al. Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American Society of Clinical Oncology clinical practice guideline. J. Clin. Oncol. 32, 3307–3329 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  249. 249.

    Schmid, P. et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 379, 2108–2121 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  250. 250.

    Marinovich, M. L. et al. Early prediction of pathologic response to neoadjuvant therapy in breast cancer: systematic review of the accuracy of MRI. Breast 21, 669–677 (2012).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  251. 251.

    Avril, S. et al. 18F-FDG PET/CT for monitoring of treatment response in breast cancer. J. Nucl. Med. 57, 34S–39SS (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  252. 252.

    Marinovich, M. L. et al. Meta-analysis of magnetic resonance imaging in detecting residual breast cancer after neoadjuvant therapy. J. Natl Cancer Inst. 105, 321–333 (2013).

    CAS  PubMed  Article  Google Scholar 

  253. 253.

    Marinovich, M. L. et al. Agreement between MRI and pathologic breast tumor size after neoadjuvant chemotherapy, and comparison with alternative tests: individual patient data meta-analysis. BMC Cancer 15, 662 (2015).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  254. 254.

    Humbert, O. et al. Role of positron emission tomography for the monitoring of response to therapy in breast cancer. Oncologist 20, 94–104 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  255. 255.

    Pennant, M. et al. A systematic review of positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) for the diagnosis of breast cancer recurrence. Health Technol. Assess. 14, 1–103 (2010).

    CAS  PubMed  Article  Google Scholar 

  256. 256.

    Shachar, S. S. Assessing treatment response in metastatic breast cancer. Am. J. Hematol. Oncol. 12, (2016).

  257. 257.

    Lee, C. I. et al. Comparative effectiveness of imaging modalities to determine metastatic breast cancer treatment response. Breast 24, 3–11 (2015).

    PubMed  Article  Google Scholar 

  258. 258.

    Pagani, O. et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N. Engl. J. Med. 371, 107–118 (2014).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  259. 259.

    Francis, P., Regan, M. & Fleming, G. Adjuvant ovarian suppression in premenopausal breast cancer. N. Engl. J. Med. 372, 1672–1673 (2015).

    Article  CAS  Google Scholar 

  260. 260.

    Mao, J. J. et al. Electroacupuncture versus gabapentin for hot flashes among breast cancer survivors: a randomized placebo-controlled trial. J. Clin. Oncol. 33, 3615–3620 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  261. 261.

    Elkins, G. et al. Randomized trial of a hypnosis intervention for treatment of hot flashes among breast cancer survivors. J. Clin. Oncol. 26, 5022–5026 (2008).

    PubMed  PubMed Central  Article  Google Scholar 

  262. 262.

    Loprinzi, C. L. et al. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet 356, 2059–2063 (2000).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  263. 263.

    Niravath, P. Aromatase inhibitor-induced arthralgia: a review. Ann. Oncol. 24, 1443–1449 (2013).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  264. 264.

    Barton, D. L. et al. Impact of vaginal dehydroepiandosterone (DHEA) on vaginal symptoms in female cancer survivors: Trial N10C1 (Alliance). J. Clin. Oncol. 32, 9507–9507 (2014).

    Article  Google Scholar 

  265. 265.

    Razvi, Y. et al. ASCO, NCCN, MASCC/ESMO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in adult patients. Support. Care Cancer 27, 87–95 (2019).

    PubMed  Article  PubMed Central  Google Scholar 

  266. 266.

    Gulati, G. et al. Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): a 2×2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur. Heart J. 37, 1671–1680 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  267. 267.

    Smith, E. M. L. et al. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA 309, 1359–1367 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  268. 268.

    Hershman, D. L. et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J. Clin. Oncol. 32, 1941–1967 (2014).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  269. 269.

    Hanai, A. et al. Effects of cryotherapy on objective and subjective symptoms of paclitaxel-induced neuropathy: prospective self-controlled trial. J. Natl Cancer Inst. 110, 141–148 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  270. 270.

    Kadakia, K. C., Rozell, S. A., Butala, A. A. & Loprinzi, C. L. Supportive cryotherapy: a review from head to toe. J. Pain Symptom Manage. 47, 1100–1115 (2014).

    PubMed  Article  PubMed Central  Google Scholar 

  271. 271.

    Hou, S., Huh, B., Kim, H. K., Kim, K.-H. & Abdi, S. Treatment of chemotherapy-induced peripheral neuropathy: systematic review and recommendations. Pain Physician 21, 571–592 (2018).

    PubMed  PubMed Central  Google Scholar 

  272. 272.

    Ahmed, R. L., Schmitz, K. H., Prizment, A. E. & Folsom, A. R. Risk factors for lymphedema in breast cancer survivors, the Iowa Women’s Health Study. Breast Cancer Res. Treat. 130, 981–991 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  273. 273.

    Gillespie, T. C., Sayegh, H. E., Brunelle, C. L., Daniell, K. M. & Taghian, A. G. Breast cancer-related lymphedema: risk factors, precautionary measures, and treatments. Gland. Surg. 7, 379–403 (2018).

    PubMed  PubMed Central  Article  Google Scholar 

  274. 274.

    Runowicz, C. D. et al. American Cancer Society/American Society of Clinical Oncology breast cancer survivorship care guideline. J. Clin. Oncol. 34, 611–635 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  275. 275.

    Velikova, G. et al. Quality of life after postmastectomy radiotherapy in patients with intermediate-risk breast cancer (SUPREMO): 2-year follow-up results of a randomised controlled trial. Lancet Oncol. 19, 1516–1529 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  276. 276.

    Hofmann, D. et al. WSG ADAPT — adjuvant dynamic marker-adjusted personalized therapy trial optimizing risk assessment and therapy response prediction in early breast cancer: study protocol for a prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III trial. Trials 14, 261 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  277. 277.

    Robertson, J. F. R., Dowsett, M. & Bliss, J. M. Peri-operative aromatase inhibitor treatment in determining or predicting long-term outcome in early breast cancer — the POETIC Trial (CRUK/07/015) [abstract]. SABCS GS1-03 (2017).

  278. 278.

    Ellis, M. J. et al. Ki67 Proliferation index as a tool for chemotherapy decisions during and after neoadjuvant aromatase inhibitor treatment of breast cancer: results from the American College of Surgeons Oncology Group Z1031 trial (Alliance). J. Clin. Oncol. 35, 1061–1069 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  279. 279.

    Hölzel, D. et al. Improved systemic treatment for early breast cancer improves cure rates, modifies metastatic pattern and shortens post-metastatic survival: 35-year results from the munich cancer registry. J. Cancer Res. Clin. Oncol. 143, 1701–1712 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  280. 280.

    Hölzel, D. et al. Survival of de novo stage IV breast cancer patients over three decades. J. Cancer Res. Clin. Oncol. 143, 509–519 (2017).

    PubMed  Article  PubMed Central  Google Scholar 

  281. 281.

    Angus, L. et al. The genomic landscape of 501 metastatic breast cancer patients [abstract]. SABCS GS1-07 (2018).

  282. 282.

    Desmedt, C. et al. Unraveling lobular breast cancer progression and endocrine resistance mechanisms through genomic and immune characterization of matched primary and metastatic samples [abstract]. SABCS GS1–06 (2018).

    Google Scholar 

  283. 283.

    Baselga, J. et al. Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 18, 904–916 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  284. 284.

    André, F. et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N. Engl. J. Med. 380, 1929–1940 (2019).

    PubMed  Article  PubMed Central  Google Scholar 

  285. 285.

    Baselga, J. et al. Phase III study of taselisib (GDC-0032) + fulvestrant (FULV) v FULV in patients (pts) with estrogen receptor (ER)-positive, PIK3CA-mutant (MUT), locally advanced or metastatic breast cancer (MBC): primary analysis from SANDPIPER. J. Clin. Oncol. 36, LBA1006–LBA1006 (2018).

    Article  Google Scholar 

  286. 286.

    Kim, S.-B. et al. Ipatasertib plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (LOTUS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 18, 1360–1372 (2017).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  287. 287.

    Schmid, P. et al. AZD5363 plus paclitaxel versus placebo plus paclitaxel as first-line therapy for metastatic triple-negative breast cancer (PAKT): a randomised, double-blind, placebo-controlled, phase II trial. J. Clin. Oncol. 36 (15 Suppl.), 1007 (2018).

    Article  Google Scholar 

  288. 288.

    Jones, R. H. et al. Capivasertib (AZD5363) plus fulvestrant versus placebo plus fulvestrant after relapse or progression on an aromatase inhibitor in metastatic ER-positive breast cancer (FAKTION): a randomized, double-blind, placebo-controlled, phase II trial [abstract]. J. Clin. Oncol. 37 (no. 15_suppl), 1005–1005 (2019).

    Article  Google Scholar 

  289. 289.

    Yardley, D. A. et al. Randomized phase II, double-blind, placebo-controlled study of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on treatment with a nonsteroidal aromatase inhibitor. J. Clin. Oncol. 31, 2128–2135 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  290. 290.

    Ogitani, Y. et al. DS-8201a, a novel HER2-targeting ADC with a novel DNA Topoisomerase I inhibitor, demonstrates a promising antitumor efficacy with differentiation from T-DM1. Clin. Cancer Res. 22, 5097–5108 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  291. 291.

    Tamura, K. et al. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 20, 816–826 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  292. 292.

    Burris III, H. A., Giaccone, G. & Im, S. A. Updated findings of a first-in-human phase 1 study of margetuximab, an Fc-optimized chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors [abstract]. Am. Soc. Clin. Oncol. Meet. 33 (no. 15_suppl), A523 (2015).

    Article  Google Scholar 

  293. 293.

    Rugo, H. S. et al. SOPHIA primary analysis: a phase 3 (P3) study of margetuximab (M) + chemotherapy (C) versus trastuzumab (T) + C in patients (pts) with HER2+ metastatic (met) breast cancer (MBC) after prior anti-HER2 therapies (Tx) [abstract]. J. Clin. Oncol. 37 (Suppl.), Abstr 1000 (2019).

    Article  Google Scholar 

  294. 294.

    Hyman, D. M., Piha-Paul, S. & Rodon, J. Neratinib in HER2- or HER3-mutant solid tumors: SUMMIT, a global, multi-histology, open-label, phase 2 ‘basket’ study [abstract]. Am. Assoc. Cancer Res. Meet. CT001 (2017).

  295. 295.

    Saura, C. et al. Neratinib + capecitabine versus lapatinib + capecitabine in patients with HER2+ metastatic breast cancer previously treated with ≥2 HER2-directed regimens: findings from the multinational, randomized, phase III NALA trial [abstract]. J. Clin. Oncol. 37 (Suppl.), Abstract 1002 (2019).

    Article  Google Scholar 

  296. 296.

    Gucalp, A. et al. Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer. Clin. Cancer Res. 19, 5505–5512 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  297. 297.

    Cortes, J., Crown, J. & Awada, A. Overall survival (OS) from the phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) signaling inhibitor, in AR+ advanced triple-negative breast cancer (aTNBC) [abstract]. Eur. Cancer Congr. 51 (Suppl. 3), 1802 (2015).

    Google Scholar 

  298. 298.

    Gelmon, K. A. et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 12, 852–861 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  299. 299.

    Nanda, R. et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 Study. J. Clin. Oncol. 34, 2460–2467 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  300. 300.

    Schmid, P., Cruz, C. & Braiteh, F. S. Atezolizumab in metastatic triple-negative breast cancer: long-term clinical outcomes and biomarker analyses [abstract]. Am. Assoc. Cancer Res. 77, A2986 (2017).

    Google Scholar 

  301. 301.

    André, F. et al. Alpelisib (ALP) + fulvestrant (FUL) for advanced breast cancer (ABC): results of the phase 3 SOLAR-1 trial [abstract]. ESMO LBA3 PR (2018).

  302. 302.

    Hyman, D. M. et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 554, 189–194 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  303. 303.

    Hartley, R. L., Stone, J. P. & Temple-Oberle, C. Breast cancer in transgender patients: a systematic review. Part 1: male to female. Eur. J. Surg. Oncol. 44, 1455–1462 (2018).

    PubMed  Article  PubMed Central  Google Scholar 

  304. 304.

    Cardoso, F. et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann. Oncol. 29, 405–417 (2017).

    PubMed Central  Google Scholar 

  305. 305.

    Di Oto, E. et al. X chromosome gain is related to increased androgen receptor expression in male breast cancer. Virchows Arch. 473, 155–163 (2018).

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  306. 306.

    Severson, T. M. & Zwart, W. A review of estrogen receptor/androgen receptor genomics in male breast cancer. Endocr. Relat. Cancer 24, R27–R34 (2017).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  307. 307.

    Deb, S. et al. PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male breast cancer. Breast Cancer Res. 15, R69 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  308. 308.

    Gucalp, A. et al. Male breast cancer: a disease distinct from female breast cancer. Breast Cancer Res. Treat. 173, 37–48 (2019).

    PubMed  Article  PubMed Central  Google Scholar 

  309. 309.

    Korde, L. A. et al. Multidisciplinary meeting on male breast cancer: summary and research recommendations. J. Clin. Oncol. 28, 2114–2122 (2010).

    PubMed  PubMed Central  Article  Google Scholar 

  310. 310.

    Cardoso, F. et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 30, 1194–1220 (2019).

    Article  Google Scholar 

  311. 311.

    Bareche, Y. et al. Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis. Ann. Oncol. 29, 895–902 (2018).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  312. 312.

    Lehmann, B. D. & Pietenpol, J. A. Clinical implications of molecular heterogeneity in triple negative breast cancer. Breast 24, S36–S40 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  313. 313.

    Lehmann, B. D. et al. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PLOS ONE 11, e0157368 (2016).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  314. 314.

    Burstein, M. D. et al. Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin. Cancer Res. 21, 1688–1698 (2015).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  315. 315.

    Siu, A. L. & on behalf of the U.S. Preventive Services Task Force. Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med. 164, 279 (2016).

    PubMed  Article  PubMed Central  Google Scholar 

  316. 316.

    Klarenbach, S. et al. Recommendations on screening for breast cancer in women aged 40–74 years who are not at increased risk for breast cancer. Can. Med. Assoc. J. 190, E1441–E1451 (2018).

    Article  Google Scholar 

  317. 317.

    Oeffinger, K. C. et al. Breast cancer screening for women at average risk: 2015 guideline update from the American Cancer Society. JAMA 314, 1599 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  318. 318.

    European Commission Initiative on Breast Cancer. Recommendations from European Breast Guidelines Europa.eu https://ecibc.jrc.ec.europa.eu/recommendations/list/Professional (2019).

  319. 319.

    Dawood, S. et al. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann. Oncol. 22, 515–523 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  320. 320.

    Cserni, G., Charafe-Jauffret, E. & van Diest, P. J. Inflammatory breast cancer: the pathologists’ perspective. Eur. J. Surg. Oncol. 44, 1128–1134 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  321. 321.

    Cheang, M. C. U. et al. Defining breast cancer intrinsic subtypes by quantitative receptor expression. Oncologist 20, 474–482 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  322. 322.

    Cancer Genome Atlas Network. Comprehensive molecular portraits of human breast tumours. Nature 490, 61–70 (2012). This research establishes the contemporary method of classifying breast cancer into clinically relevant molecular subtypes.

    Article  CAS  Google Scholar 

  323. 323.

    Hoadley, K. A., Andre, F., Ellis, M. J. & Perou, C. M. Breast cancer intrinsic subtypes (Poster). Nat. Rev. Clin. Oncol. https://www.nature.com/documents/nrclinonc_posters_breastcancer.pdf (2014).

  324. 324.

    Desmedt, C. et al. Genomic characterization of primary invasive lobular breast cancer. J. Clin. Oncol. 34, 1872–1881 (2016).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  325. 325.

    Ciriello, G. et al. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 163, 506–519 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  326. 326.

    Vasudev, P. & Onuma, K. Secretory breast carcinoma: unique, triple-negative carcinoma with a favorable prognosis and characteristic molecular expression. Arch. Pathol. Lab. Med. 135, 1606–1610 (2011).

    PubMed  Article  PubMed Central  Google Scholar 

  327. 327.

    Martelotto, L. G. et al. Genomic landscape of adenoid cystic carcinoma of the breast. J. Pathol. 237, 179–189 (2015).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  328. 328.

    Goss, P. E. et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N. Engl. J. Med. 375, 209–219 (2016).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  329. 329.

    Liang, M. et al. Association between CHEK2*1100delC and breast cancer: a systematic review and meta-analysis. Mol. Diagn. Ther. 22, 397–407 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  330. 330.

    Wang, X. et al. Breast cancer risk and germline genomic profiling of women with neurofibromatosis type 1 who developed breast cancer. Genes. Chromosomes Cancer 57, 19–27 (2018).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  331. 331.

    McCart Reed, A. E. et al. Phenotypic and molecular dissection of metaplastic breast cancer and the prognostic implications: prognostic features of metaplastic breast cancer. J. Pathol. 247, 214–227 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  332. 332.

    Wendt, C. & Margolin, S. Identifying breast cancer susceptibility genes — a review of the genetic background in familial breast cancer. Acta Oncol. 58, 135–146 (2019).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  333. 333.

    Couch, F. J. et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 3, 1190 (2017).

    PubMed  PubMed Central  Article  Google Scholar 

  334. 334.

    Nguyen, J. et al. EORTC QLQ-BR23 and FACT-B for the assessment of quality of life in patients with breast cancer: a literature review. J. Comp. Eff. Res. 4, 157–166 (2015).

    PubMed  Article  PubMed Central  Google Scholar 

  335. 335.

    McLachlan, S. A., Devins, G. M. & Goodwin, P. J. Factor analysis of the psychosocial items of the EORTC QLQ-C30 in metastatic breast cancer patients participating in a psychosocial intervention study. Qual. Life Res. 8, 311–317 (1999).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  336. 336.

    Bjelic-Radisic, V. et al. An international update of the EORTC questionnaire for assessing quality of life in breast cancer patients (EORTC QLQ-BC23) — EORTC QLQ-BR45. Ann. Oncol. 29, viii58–viii86 (2018).

    Article  Google Scholar 

  337. 337.

    Ganz, P. A., Kwan, L., Stanton, A. L., Bower, J. E. & Belin, T. R. Physical and psychosocial recovery in the year after primary treatment of breast cancer. J. Clin. Oncol. 29, 1101–1109 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  338. 338.

    Revicki, D. A. et al. Predicting EuroQol (EQ-5D) scores from the patient-reported outcomes measurement information system (PROMIS) global items and domain item banks in a United States sample. Qual. Life Res. 18, 783–791 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  339. 339.

    Hays, R. D., Bjorner, J. B., Revicki, D. A., Spritzer, K. L. & Cella, D. Development of physical and mental health summary scores from the patient-reported outcomes measurement information system (PROMIS) global items. Qual. Life Res. 18, 873–880 (2009).

    PubMed  PubMed Central  Article  Google Scholar 

  340. 340.

    Bevans, M., Ross, A. & Cella, D. Patient-reported outcomes measurement information system (PROMIS): efficient, standardized tools to measure self-reported health and quality of life. Nurs. Outlook 62, 339–345 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

Download references

Acknowledgements

The authors thank N. Radosevic-Robin (Jean Perrin Comprehensive Cancer Centre, France) for her assistance in preparing Fig. 1. N. Houssami receives research support through a National Breast Cancer Foundation (NBCF, Australia) Breast Cancer Research Leadership Fellowship. K.R. acknowledges research funding from the Clinical and Translational Sciences Award (CTSA) grant number KL2 TR002379 from the National Centre for Advancing Translational Sciences, a component of the US National Institutes of Health.

Author information

Affiliations

Authors

Contributions

Introduction (all authors); Epidemiology (J.T.); Mechanisms/pathophysiology (F.P.-L.); Diagnosis, screening and prevention (N. Houssami); Management (N. Harbeck, F.C., M.G., P.P., J.C. and N. Houssami); Quality of life (K.R.); Outlook (all authors); Overview of the Primer (N. Harbeck and F.C.).

Corresponding author

Correspondence to Nadia Harbeck.

Ethics declarations

Competing interests

N. Harbeck reports honoraria for lectures and/or consulting from Agendia, Amgen, Astra Zeneca, Celgene, Daiichi-Sankyo, Genomic Health, Lilly, MSD, Novartis, Odonate, Pfizer, Roche, Sandoz/Hexal and Seattle Genetics. F.P.-L. declares personal financial interests in Abbvie, Agendia, Astrazeneca, BMS, Genomic Health, Janssen, Lilly, Merck Lifa, MSD, Myriad, Nanostring, Novartis, Pfizer and Roche; institutional financial interests in Astrazeneca, BMS, Genomic Health, MSD, Myriad, Nanostring and Roche; and congress invitations from Abbvie, Astrazeneca, BMS, MSD and Roche. J.C. has received honoraria from Celgene, Chugai, Eisai, Novartis, Pfizer, Roche and Samsung; has served as a consultant for Astrazeneca, Biothera, Celgene, Daichii Sankyo, Erytech Pharma, Merus, Polyphor, Roche and Seattle Genetics; has received research funding from Ariad, Astrazeneca, Baxalta GMBH, Bayer, Eisai, Guardant Health, Merch Sharp & Dohme, Pfizer, Puma and Roche; and has stocks in MedSIR. M.G. reports honoraria from Amgen, AstraZeneca, Celgene, Eli Lilly, Medison, Nanostring Technologies, Novartis and Roche; advisory fees from Accelsoir; research funding from AstraZeneca, Novartis, Pfizer and Roche; and travel expenses from Amgen, AstraZeneca, Celgene, Eli Lilly, Ipsen, Medison, Novartis and Pfizer. K.R. declares previous ownership of Merck and Pfizer stock (October 2016–February 2018). J.T. reports honoraria and consultancy or advisory roles for AstraZeneca, Astellas, De Novo, Eisai, Foundation Medicine, Nanostring, Novartis, Pfizer and Roche. F.C. declares consultancy roles for Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, Genentech, GE Oncology, GlaxoSmithKline, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanofi, Seattle Genetics and Teva. The remaining authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Disease Primers thanks T. Howell, P. Neven, M. Toi and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

ABC Global Alliance: https://www.abcglobalalliance.org

Adjuvant! Online: www.adjuvantonline.com

European Organization for Research and Treatment of Cancer: https://qol.eortc.org/modules/

EuroQol 5-Dimensions: https://euroqol.org/

Functional Assessment of Cancer Therapy: http://www.facit.org/FACITOrg

Patient-Reported Outcomes Measurement Information System: http://www.healthmeasures.net/explore-measurement-systems/promis

Short Form Health Survey-36: http://www.rand.org/health/surveys_tools/mos/36-item-short-form.html

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Harbeck, N., Penault-Llorca, F., Cortes, J. et al. Breast cancer. Nat Rev Dis Primers 5, 66 (2019). https://doi.org/10.1038/s41572-019-0111-2

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing