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.
Subscribe to Journal
Get full journal access for 1 year
only $59.00 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).
Cardoso, F. et al. European Breast Cancer Conference manifesto on breast centres/units. Eur. J. Cancer 72, 244–250 (2017).
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).
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).
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).
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).
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).
Ginsburg, O. et al. The global burden of women’s cancers: a grand challenge in global health. Lancet 389, 847–860 (2017).
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).
Winters, S., Martin, C., Murphy, D. & Shokar, N. K. Breast cancer epidemiology, prevention, and screening. Prog. Mol. Biol. Transl Sci. 151, 1–32 (2017).
Hossain, M. S., Ferdous, S. & Karim-Kos, H. E. Breast cancer in South. Asia: a Bangladeshi perspective. Cancer Epidemiol. 38, 465–470 (2014).
Leong, S. P. L. et al. Is breast cancer the same disease in Asian and western countries? World J. Surg. 34, 2308–2324 (2010).
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).
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).
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).
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).
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).
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).
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).
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).
Shiovitz, S. & Korde, L. A. Genetics of breast cancer: a topic in evolution. Ann. Oncol. 26, 1291–1299 (2015).
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).
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).
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).
Kuchenbaecker, K. B. et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. JAMA 317, 2402 (2017).
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).
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).
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).
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).
Robson, M. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 377, 523–533 (2017).
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).
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).
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).
Pasche, B. Recent advances in breast cancer genetics. Cancer Treat. Res. 141, 1–10 (2008).
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).
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).
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).
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).
Colditz, G. A., Sellers, T. A. & Trapido, E. Epidemiology — identifying the causes and preventability of cancer? Nat. Rev. Cancer 6, 75–83 (2006).
Britt, K., Ashworth, A. & Smalley, M. Pregnancy and the risk of breast cancer. Endocr. Relat. Cancer 14, 907–933 (2007).
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).
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).
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).
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).
Singletary, K. W. & Gapstur, S. M. Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms. JAMA 286, 2143 (2001).
Smith-Warner, S. A. et al. Alcohol and breast cancer in women: a pooled analysis of cohort studies. JAMA 279, 535 (1998).
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).
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).
Shieh, Y. et al. Body mass index, mammographic density, and breast cancer risk by estrogen receptor subtype. Breast Cancer Res. 21, 48 (2019).
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).
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).
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).
Mørch, L. S. et al. Contemporary hormonal contraception and the risk of breast cancer. N. Engl. J. Med. 377, 2228–2239 (2017).
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).
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).
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).
Bodai, B. Breast cancer survivorship: a comprehensive review of long-term medical issues and lifestyle recommendations. Perm. J. 19, 48–79 (2015).
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).
Miyashita, M. et al. Unmet information needs and quality of life in young breast cancer survivors in japan. Cancer Nurs. 38, E1–E11 (2015).
Bombonati, A. & Sgroi, D. C. The molecular pathology of breast cancer progression. J. Pathol. 223, 307–317 (2011).
Ellis, M. J. et al. Whole-genome analysis informs breast cancer response to aromatase inhibition. Nature 486, 353–360 (2012).
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).
Nik-Zainal, S. et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534, 47–54 (2016).
Yates, L. R. & Desmedt, C. Translational genomics: practical applications of the genomic revolution in breast cancer. Clin. Cancer Res. 23, 2630–2639 (2017).
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).
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).
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).
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).
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).
Williams, C. & Lin, C.-Y. Oestrogen receptors in breast cancer: basic mechanisms and clinical implications. Ecancermedicalscience 7, 370 (2013).
Levin, E. R. & Pietras, R. J. Estrogen receptors outside the nucleus in breast cancer. Breast Cancer Res. Treat. 108, 351–361 (2008).
Santen, R. J. Clinical review: effect of endocrine therapies on bone in breast cancer patients. J. Clin. Endocrinol. Metab. 96, 308–319 (2011).
Ruffell, B. et al. Leukocyte composition of human breast cancer. Proc. Natl Acad. Sci. USA 109, 2796–2801 (2012).
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).
Nagarajan, D. & McArdle, S. Immune landscape of breast cancers. Biomedicines 6, 20 (2018).
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).
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).
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).
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).
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).
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).
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).
Santé Publique France. Breast cancer [French]. Santepubliquefrance.fr https://www.santepubliquefrance.fr/maladies-et-traumatismes/cancers/cancer-du-sein (2019).
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).
Yates, L. R. et al. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell 32, 169–184.e7 (2017).
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).
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).
Independent, U. K. Panel on breast cancer screening. the benefits and harms of breast cancer screening: an independent review. Lancet 380, 1778–1786 (2012).
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).
Lauby-Secretan, B. et al. Breast-cancer screening — viewpoint of the IARC Working Group. N. Engl. J. Med. 372, 2353–2358 (2015).
Houssami, N. Overdiagnosis of breast cancer in population screening: does it make breast screening worthless? Cancer Biol. Med. 14, 1–8 (2017).
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).
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).
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).
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).
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).
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).
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).
Sardanelli, F. et al. Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. Eur. J. Cancer 46, 1296–1316 (2010).
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).
Houssami, N. & Lee, C. I. The impact of legislation mandating breast density notification — review of the evidence. Breast 42, 102–112 (2018).
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).
Irwig, L., Macaskill, P. & Houssami, N. Evidence relevant to the investigation of breast symptoms: the triple test. Breast 11, 215–220 (2002).
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).
Morrow, M., Waters, J. & Morris, E. MRI for breast cancer screening, diagnosis, and treatment. Lancet 378, 1804–1811 (2011).
Srigley, J. R. et al. Standardized synoptic cancer pathology reporting: a population-based approach. J. Surg. Oncol. 99, 517–524 (2009).
World Heath Organisation. WHO Classification of Tumours of the Breast, Fourth Edition. (World Health Organization, 2012).
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).
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).
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).
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).
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).
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).
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).
Rakha, E. A. et al. The prognostic significance of lymphovascular invasion in invasive breast carcinoma. Cancer 118, 3670–3680 (2012).
Barrio, A. V. & Morrow, M. Appropriate margin for lumpectomy excision of invasive breast cancer. Chin. Clin. Oncol. 5, 35–35 (2016).
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).
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).
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).
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).
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).
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).
Tao, L. et al. Breast cancer mortality in older and younger breast cancer patients in California. Cancer Epidemiol. Biomark. Prev. 28, 303–310 (2018).
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).
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).
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).
Phung, M. T., Tin Tin, S. & Elwood, J. M. Prognostic models for breast cancer: a systematic review. BMC Cancer 19, 230 (2019).
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).
Cortazar, P. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 384, 164–172 (2014).
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).
Sparano, J. A. et al. Prospective validation of a 21-gene expression assay in breast cancer. N. Engl. J. Med. 373, 2005–2014 (2015).
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).
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).
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).
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).
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).
McLaughlin, S. A. Surgical management of the breast: breast conservation therapy and mastectomy. Surg. Clin. North Am. 93, 411–428 (2013).
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).
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).
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).
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.
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).
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).
Haloua, M. H. et al. A systematic review of oncoplastic breast-conserving surgery: current weaknesses and future prospects. Ann. Surg. 257, 609–620 (2013).
Benelli, L. A new periareolar mammaplasty: the ‘round block’ technique. Aesthetic Plast. Surg. 14, 93–100 (1990).
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).
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).
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).
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).
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.
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).
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).
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).
Kaidar-Person, O., Meattini, I. & Poortmans, P. M. P. Between uncertainties and overtreatment. Int. J. Radiat. Oncol. 104, 15–16 (2019).
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).
King, T. A. & Morrow, M. Surgical issues in patients with breast cancer receiving neoadjuvant chemotherapy. Nat. Rev. Clin. Oncol. 12, 335–343 (2015).
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).
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.
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.
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).
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).
Poortmans, P. Postmastectomy radiation in breast cancer with one to three involved lymph nodes: ending the debate. Lancet 383, 2104–2106 (2014).
Poortmans, P. M. et al. Internal mammary and medial supraclavicular irradiation in breast cancer. N. Engl. J. Med. 373, 317–327 (2015).
Whelan, T. J. et al. Regional nodal irradiation in early-stage breast cancer. N. Engl. J. Med. 373, 307–316 (2015).
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).
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).
Oliai, C. & Hurvitz, S. A. The debate over post-mastectomy radiotherapy should continue: breast cancer. Nat. Rev. Clin. Oncol. 12, 567–568 (2015).
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).
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).
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).
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).
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).
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).
Poortmans, P. M. P., Arenas, M. & Livi, L. Over-irradiation. Breast 31, 295–302 (2017).
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).
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).
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).
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).
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).
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).
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).
Whelan, T. J. et al. Long-term results of hypofractionated radiation therapy for breast cancer. N. Engl. J. Med. 362, 513–520 (2010).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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.
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).
Francis, P. A. et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N. Engl. J. Med. 379, 122–137 (2018).
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).
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.
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).
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).
Finn, R. S. et al. Palbociclib and letrozole in advanced breast cancer. N. Engl. J. Med. 375, 1925–1936 (2016).
Hortobagyi, G. N. et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N. Engl. J. Med. 375, 1738–1748 (2016).
Goetz, M. P. et al. MONARCH 3: abemaciclib as initial therapy for advanced breast cancer. J. Clin. Oncol. 35, 3638–3646 (2017).
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).
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).
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).
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).
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).
von Minckwitz, G. et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N. Engl. J. Med. 380, 617–628 (2018).
von Minckwitz, G. et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N. Engl. J. Med. 377, 122–131 (2017).
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).
Tolaney, S. M. et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N. Engl. J. Med. 372, 134–141 (2015).
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).
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).
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).
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).
Piccart-Gebhart, M. J. et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N. Engl. J. Med. 353, 1659–1672 (2005).
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).
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).
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).
Masuda, N. et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N. Engl. J. Med. 376, 2147–2159 (2017).
Gnant, M. et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet 386, 433–443 (2015).
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).
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).
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).
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).
Cardoso, F. et al. 4th ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 4)†. Ann. Oncol. 29, 1634–1657 (2018).
Golse, N. & Adam, R. Liver metastases from breast cancer: what role for surgery? Indications and results. Clin. Breast Cancer 17, 256–265 (2017).
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).
Shien, T. & Doihara, H. Resection of the primary tumor in stage IV breast cancer. World J. Clin. Oncol. 5, 82–85 (2014).
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).
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).
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).
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).
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).
Cameron, D. Removing the primary tumour in metastatic breast cancer. Lancet Oncol. 16, 1284–1285 (2015).
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).
Phillips, C., Jeffree, R. & Khasraw, M. Management of breast cancer brain metastases: a practical review. Breast 31, 90–98 (2017).
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).
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).
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).
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).
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).
Bernier, J. Immuno-oncology: allying forces of radio- and immuno-therapy to enhance cancer cell killing. Crit. Rev. Oncol. Hematol. 108, 97–108 (2016).
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).
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).
Turner, N. C. et al. Overall survival with palbociclib and fulvestrant in advanced breast cancer. N. Engl. J. Med. 379, 1926–1936 (2018).
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).
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).
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).
Schmid, P. et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 379, 2108–2121 (2018).
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).
Avril, S. et al. 18F-FDG PET/CT for monitoring of treatment response in breast cancer. J. Nucl. Med. 57, 34S–39SS (2016).
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).
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).
Humbert, O. et al. Role of positron emission tomography for the monitoring of response to therapy in breast cancer. Oncologist 20, 94–104 (2015).
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).
Shachar, S. S. Assessing treatment response in metastatic breast cancer. Am. J. Hematol. Oncol. 12, (2016).
Lee, C. I. et al. Comparative effectiveness of imaging modalities to determine metastatic breast cancer treatment response. Breast 24, 3–11 (2015).
Pagani, O. et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N. Engl. J. Med. 371, 107–118 (2014).
Francis, P., Regan, M. & Fleming, G. Adjuvant ovarian suppression in premenopausal breast cancer. N. Engl. J. Med. 372, 1672–1673 (2015).
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).
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).
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).
Niravath, P. Aromatase inhibitor-induced arthralgia: a review. Ann. Oncol. 24, 1443–1449 (2013).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Angus, L. et al. The genomic landscape of 501 metastatic breast cancer patients [abstract]. SABCS GS1-07 (2018).
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).
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).
André, F. et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N. Engl. J. Med. 380, 1929–1940 (2019).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Hyman, D. M. et al. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature 554, 189–194 (2018).
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).
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).
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).
Severson, T. M. & Zwart, W. A review of estrogen receptor/androgen receptor genomics in male breast cancer. Endocr. Relat. Cancer 24, R27–R34 (2017).
Deb, S. et al. PIK3CA mutations are frequently observed in BRCAX but not BRCA2-associated male breast cancer. Breast Cancer Res. 15, R69 (2013).
Gucalp, A. et al. Male breast cancer: a disease distinct from female breast cancer. Breast Cancer Res. Treat. 173, 37–48 (2019).
Korde, L. A. et al. Multidisciplinary meeting on male breast cancer: summary and research recommendations. J. Clin. Oncol. 28, 2114–2122 (2010).
Cardoso, F. et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 30, 1194–1220 (2019).
Bareche, Y. et al. Unravelling triple-negative breast cancer molecular heterogeneity using an integrative multiomic analysis. Ann. Oncol. 29, 895–902 (2018).
Lehmann, B. D. & Pietenpol, J. A. Clinical implications of molecular heterogeneity in triple negative breast cancer. Breast 24, S36–S40 (2015).
Lehmann, B. D. et al. Refinement of triple-negative breast cancer molecular subtypes: implications for neoadjuvant chemotherapy selection. PLOS ONE 11, e0157368 (2016).
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).
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).
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).
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).
European Commission Initiative on Breast Cancer. Recommendations from European Breast Guidelines Europa.eu https://ecibc.jrc.ec.europa.eu/recommendations/list/Professional (2019).
Dawood, S. et al. International expert panel on inflammatory breast cancer: consensus statement for standardized diagnosis and treatment. Ann. Oncol. 22, 515–523 (2011).
Cserni, G., Charafe-Jauffret, E. & van Diest, P. J. Inflammatory breast cancer: the pathologists’ perspective. Eur. J. Surg. Oncol. 44, 1128–1134 (2018).
Cheang, M. C. U. et al. Defining breast cancer intrinsic subtypes by quantitative receptor expression. Oncologist 20, 474–482 (2015).
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.
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).
Desmedt, C. et al. Genomic characterization of primary invasive lobular breast cancer. J. Clin. Oncol. 34, 1872–1881 (2016).
Ciriello, G. et al. Comprehensive molecular portraits of invasive lobular breast cancer. Cell 163, 506–519 (2015).
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).
Martelotto, L. G. et al. Genomic landscape of adenoid cystic carcinoma of the breast. J. Pathol. 237, 179–189 (2015).
Goss, P. E. et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N. Engl. J. Med. 375, 209–219 (2016).
Liang, M. et al. Association between CHEK2*1100delC and breast cancer: a systematic review and meta-analysis. Mol. Diagn. Ther. 22, 397–407 (2018).
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).
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).
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).
Couch, F. J. et al. Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncol. 3, 1190 (2017).
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).
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).
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).
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).
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).
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).
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).
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.
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.
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.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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
About this article
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
Genes & Diseases (2021)
Advanced Therapeutics (2021)
Journal of Cancer Education (2021)
The Prognostic Significance of Anisomycin-Activated Phospho-c-Jun NH2-Terminal Kinase (p-JNK) in Predicting Breast Cancer Patients’ Survival Time
Frontiers in Cell and Developmental Biology (2021)
M2‐Like TAMs Function Reversal Contributes to Breast Cancer Eradication by Combination Dual Immune Checkpoint Blockade and Photothermal Therapy