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.

Epidemiology

Clinicopathological features and BRCA1 and BRCA2 mutation status in a prospective cohort of young women with breast cancer

Subjects

Abstract

Background

Breast cancer in young women is more likely to have higher risk features and be associated with germline BRCA1/BRCA2 mutations. We present the clinicopathologic features of breast cancers in a prospective cohort of young women, and associations between surrogate molecular subtype and BRCA1/BRCA2 mutation status.

Methods

Histopathological features, biomarker status, tumour stage and BRCA status were collected. Invasive tumours were categorised as luminal A-like (ER + and/or PR + , HER2−, grade 1/2), luminal B-like (ER + and/or PR + , HER2 + , or ER + and/or PR + , HER2−, and grade 3), HER2-enriched (ER/PR−, HER2 + ) or triple-negative.

Results

In all, 57.3% (654/1143) of invasive tumours were high grade. In total, 32.9% were luminal A-like, 42.4% luminal B-like, 8.3% HER2-enriched, and 16.4% triple-negative. Among different age groups, there were no differences in molecular phenotype, stage, grade or histopathology. 11% (131) of tumours were from BRCA mutation carriers; 64.1% BRCA1 (63.1% triple-negative), and 35.9% BRCA2 (55.3% luminal B-like).

Discussion

The opportunity to provide comparisons across young age groups, BRCA mutation status, surrogate molecular phenotype, and the identification of more aggressive hormone receptor-positive phenotypes in this population provides direction for future work to further understand and improve disparate outcomes for young women with luminal B-like cancers, particularly BRCA2-associated cancers, with potential implications for tailored prevention and treatment.

This is a preview of subscription content

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: Profile of study population.
Fig. 2: Distribution of molecular phenotypes among BRCA1 + , BRCA2 + , no mutation detected/VUS, and not tested.

Data availability

Available from the corresponding author on reasonable request.

References

  1. 1.

    Fidler MM, Gupta S, Soerjomataram I, Ferlay J, Steliarova-Foucher E, Bray F. Cancer incidence and mortality among young adults aged 20-39 years worldwide in 2012: a population-based study. Lancet Oncol. 2017;18:1579–89.

    PubMed  Article  PubMed Central  Google Scholar 

  2. 2.

    Thomas A, Rhoads A, Pinkerton E, Schroeder MC, Conway KM, Hundley WG, et al. Incidence and survival among young women with stage I-III breast cancer: SEER 2000-2015. JNCI Cancer Spectr. 2019;3:pkz040.

    PubMed  PubMed Central  Article  Google Scholar 

  3. 3.

    Johnson RH, Chien FL, Bleyer A. Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009. J Am Med Assoc. 2013;309:800–5.

    CAS  Article  Google Scholar 

  4. 4.

    Azim HA, Michiels S, Bedard PL, Singhal SK, Criscitiello C, Ignatiadis M, et al. Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling. Clin Cancer Res. 2012;18:1341–51.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  5. 5.

    Partridge AH, Hughes ME, Warner ET, Ottesen RA, Wong YN, Edge SB, et al. Subtype-dependent relationship between young age at diagnosis and breast cancer survival. J Clin Oncol. 2016;34:3308–14.

    PubMed  Article  Google Scholar 

  6. 6.

    Keegan TH, DeRouen MC, Press DJ, Kurian AW, Clarke CA. Occurrence of breast cancer subtypes in adolescent and young adult women. Breast Cancer Res. 2012;14:R55.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7.

    Azim HA, Partridge AH. Biology of breast cancer in young women. Breast Cancer Res. 2014;16:427.

    PubMed  PubMed Central  Article  Google Scholar 

  8. 8.

    Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. J Am Med Assoc 2006;295:2492–502.

    CAS  Article  Google Scholar 

  9. 9.

    Allott EH, Geradts J, Cohen SM, Khoury T, Zirpoli GR, Bshara W, et al. Frequency of breast cancer subtypes among African American women in the AMBER consortium. Breast Cancer Res. 2018;20:12.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  10. 10.

    Liu Z, Sahli Z, Wang Y, Wolff AC, Cope LM, Umbricht CB. Young age at diagnosis is associated with worse prognosis in the Luminal A breast cancer subtype: a retrospective institutional cohort study. Breast Cancer Res Treat. 2018;172:689–702.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Lian W, Fu F, Lin Y, Lu M, Chen B, Yang P, et al. The impact of young age for prognosis by subtype in women with early breast cancer. Sci Rep. 2017;7:11625.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  12. 12.

    Liu W, Xiong XF, Mo YZ, Chen WG, Li M, Liang R, et al. Young age at diagnosis is associated with better prognosis in stage IV breast cancer. Aging. 2019;11:11382–90.

    PubMed  PubMed Central  Article  Google Scholar 

  13. 13.

    King MC, Marks JH, Mandell JB. Group NYBCS. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302:643–6.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1998;62:676–89.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. 15.

    Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet. 1995;56:265–71.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Huzarski T, Byrski T, Gronwald J, Górski B, Domagala P, Cybulski C, et al. Ten-year survival in patients with BRCA1-negative and BRCA1-positive breast cancer. J Clin Oncol. 2013;31:3191–6.

    PubMed  Article  Google Scholar 

  17. 17.

    Young SR, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, et al. The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer. 2009;9:86.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. 18.

    Gewefel H, Salhia B. Breast cancer in adolescent and young adult women. Clin Breast Cancer. 2014;14:390–5.

    PubMed  Article  PubMed Central  Google Scholar 

  19. 19.

    Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst. 1999;91:943–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  20. 20.

    Ha SM, Chae EY, Cha JH, Kim HH, Shin HJ, Choi WJ. Association of BRCA mutation types, imaging features, and pathologic findings in patients with breast cancer with BRCA1 and BRCA2 mutations. AJR Am J Roentgenol. 2017;209:920–8.

    PubMed  Article  Google Scholar 

  21. 21.

    Larsen MJ, Kruse TA, Tan Q, Lænkholm AV, Bak M, Lykkesfeldt AE, et al. Classifications within molecular subtypes enables identification of BRCA1/BRCA2 mutation carriers by RNA tumor profiling. PLoS ONE. 2013;8:e64268.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22.

    Copson ER, Maishman TC, Tapper WJ, Cutress RI, Greville-Heygate S, Altman DG, et al. Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study. Lancet Oncol. 2018;19:169–80.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Toss A, Molinaro E, Venturelli M, Domati F, Marcheselli L, Piana S, et al. BRCA detection rate in an Italian Cohort of luminal early-onset and triple-negative breast cancer patients without family history: when biology overcomes genealogy. Cancers. 2020;12:1252.

  24. 24.

    Arun B, Bayraktar S, Liu DD, Gutierrez Barrera AM, Atchley D, Pusztai L, et al. Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation carriers and noncarriers: a single-institution experience. J Clin Oncol. 2011;29:3739–46.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  25. 25.

    Collins LC, Marotti JD, Gelber S, Cole K, Ruddy K, Kereakoglow S, et al. Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer. Breast Cancer Res Treat. 2012;131:1061–6.

    CAS  PubMed  Article  Google Scholar 

  26. 26.

    Poorvu PD, Gelber SI, Rosenberg SM, Ruddy KJ, Tamimi RM, Collins LC, et al. Prognostic impact of the 21-gene recurrence score assay among young women with node-negative and node-positive ER-positive/HER2-negative breast cancer. J Clin Oncol. 2020;38:725–33.

    CAS  PubMed  Article  Google Scholar 

  27. 27.

    Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 2008;14:1368–76.

    CAS  PubMed  Article  Google Scholar 

  28. 28.

    Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst. 2009;101:736–50.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. 29.

    Tamimi RM, Baer HJ, Marotti J, Galan M, Galaburda L, Fu Y, et al. Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Res. 2008;10:R67.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  30. 30.

    Yang XR, Sherman ME, Rimm DL, Lissowska J, Brinton LA, Peplonska B, et al. Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomark Prev. 2007;16:439–43.

    CAS  Article  Google Scholar 

  31. 31.

    Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z, et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res. 2004;10:5367–74.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, et al. Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22:1736–47.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. 33.

    Evans DG, van Veen EM, Byers HJ, Evans SJ, Burghel GJ, Woodward ER, et al. High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer. J Med Genet. 2021;1–7.

  34. 34.

    Mavaddat N, Barrowdale D, Andrulis IL, Domchek SM, Eccles D, Nevanlinna H, et al. Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomark Prev. 2012;21:134–47.

    CAS  Article  Google Scholar 

  35. 35.

    Shah PD, Patil S, Dickler MN, Offit K, Hudis CA, Robson ME. Twenty-one-gene recurrence score assay in BRCA-associated versus sporadic breast cancers: differences based on germline mutation status. Cancer 2016;122:1178–84.

    CAS  PubMed  Article  Google Scholar 

  36. 36.

    Spurdle AB, Couch FJ, Parsons MT, McGuffog L, Barrowdale D, Bolla MK, et al. Refined histopathological predictors of BRCA1 and BRCA2 mutation status: a large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia. Breast Cancer Res. 2014;16:3419.

    PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips KA, Mooij TM, Roos-Blom MJ, et al. Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Am Med Assoc. 2017;317:2402–16.

    CAS  Article  Google Scholar 

  38. 38.

    Jonasson JG, Stefansson OA, Johannsson OT, Sigurdsson H, Agnarsson BA, Olafsdottir GH, et al. Oestrogen receptor status, treatment and breast cancer prognosis in Icelandic BRCA2 mutation carriers. Br J Cancer. 2016;115:776–83.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. 39.

    Kotsopoulos J, Singer C, Narod SA. Can we prevent BRCA1-associated breast cancer by RANKL inhibition? Breast Cancer Res Treat. 2017;161:11–6.

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Nolan E, Vaillant F, Branstetter D, Pal B, Giner G, Whitehead L, et al. RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. Nat Med. 2016;22:933–9.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  41. 41.

    Kotsopoulos J, Huzarski T, Gronwald J, Singer CF, Moller P, Lynch HT, et al. Bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2017;109.

  42. 42.

    Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. J Am Med Assoc. 2010;304:967–75.

    CAS  Article  Google Scholar 

  43. 43.

    Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, Garber JE, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol. 2008;26:1331–7.

    PubMed  Article  PubMed Central  Google Scholar 

  44. 44.

    Rebbeck TR, Friebel T, Wagner T, Lynch HT, Garber JE, Daly MB, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2005;23:7804–10.

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  45. 45.

    Mavaddat N, Antoniou AC, Mooij TM, Hooning MJ, Heemskerk-Gerritsen BA, Noguès C, et al. Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers. Breast Cancer Res. 2020;22:8.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Litton JK, Rugo HS, Ettl J, Hurvitz SA, Gonçalves A, Lee KH, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N. Engl J Med. 2018;379:753–63.

    CAS  PubMed  Article  Google Scholar 

  47. 47.

    Cancello G, Maisonneuve P, Rotmensz N, Viale G, Mastropasqua MG, Pruneri G, et al. Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. Ann Oncol. 2010;21:1974–81.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Schaffar R, Bouchardy C, Chappuis PO, Bodmer A, Benhamou S, Rapiti E. A population-based cohort of young women diagnosed with breast cancer in Geneva, Switzerland. PLoS ONE. 2019;14:e0222136.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Franzoi MA, Rosa DD, Zaffaroni F, Werutsky G, Simon S, Bines J, et al. Advanced stage at diagnosis and worse clinicopathologic features in young women with breast cancer in Brazil: a subanalysis of the AMAZONA III study (GBECAM 0115). J Glob Oncol. 2019;5:1–10.

    PubMed  Article  Google Scholar 

  50. 50.

    Anders CK, Fan C, Parker JS, Carey LA, Blackwell KL, Klauber-DeMore N, et al. Breast carcinomas arising at a young age: unique biology or a surrogate for aggressive intrinsic subtypes? J Clin Oncol. 2011;29:e18–20.

    PubMed  Article  Google Scholar 

  51. 51.

    Morrison DH, Rahardja D, King E, Peng Y, Sarode VR. Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer. Br J Cancer. 2012;107:382–7.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Cherbal F, Gaceb H, Mehemmai C, Saiah I, Bakour R, Rouis AO, et al. Distribution of molecular breast cancer subtypes among Algerian women and correlation with clinical and tumor characteristics: a population-based study. Breast Dis. 2015;35:95–102.

    PubMed  Article  Google Scholar 

  53. 53.

    Walsh T, Gulsuner S, Lee MK, Troester MA, Olshan AF, Earp HS, et al. Inherited predisposition to breast cancer in the Carolina Breast Cancer Study. NPJ Breast Cancer. 2021;7:6.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Collins LC, Marotti JD, Baer HJ, Tamimi RM. Comparison of estrogen receptor results from pathology reports with results from central laboratory testing. J Natl Cancer Inst. 2008;100:218–21.

    CAS  PubMed  Article  Google Scholar 

  55. 55.

    Hu C, Polley EC, Yadav S, Lilyquist J, Shimelis H, Na J, et al. The contribution of germline predisposition gene mutations to clinical subtypes of invasive breast cancer from a clinical genetic testing cohort. J Natl Cancer Inst. 2020;12:1231–41.

  56. 56.

    Guzman-Arocho YD, Rosenberg SM, Poorvu P, Ruddy KJ, Kirkner G, Snow C, et al. Clinicopathological features and BRCA 1/2 status in a large prospective cohort of young women with breast cancer. Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TC. AACR; Cancer Res. 2020;80 (4 Suppl):Abstract P4-07-02.

Download references

Acknowledgements

Abstract presented at the annual meeting of San Antonio Breast Cancer Symposium 2019 [56].

Funding

This work was supported by the Susan G. Komen Foundation and Breast Cancer Research Foundation.

Author information

Affiliations

Authors

Contributions

Study design and methodology: SMR, AHP and LCC. Data collection: YDGA, HV, CS, JDM and LCC. Data analysis and interpretation: YDGA, SMR, GK, AHP and LCC. Drafting manuscript: YDGA, SMR, AHP and LCC. Critical revisions: SMR, JEG, PDP, KJR, RMT, LS, VFR, SEC, EFB, JDM, EW, AHP and LCC. All the authors approved the final version.

Corresponding author

Correspondence to Laura C. Collins.

Ethics declarations

Ethics approval and consent to participate

Institutional review board (IRB) approval for the study was obtained through the Dana–Farber/Harvard Cancer Centre and other participating centres. The study was performed in accordance with the Declaration of Helsinki and informed written consent was obtained from all the participants.

Consent to publish

Not applicable.

Competing interests

Dr. Rulla Tamimi is an editor of the British Journal of Cancer. The remaining authors declare no competing interests.

Additional information

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

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Guzmán-Arocho, Y.D., Rosenberg, S.M., Garber, J.E. et al. Clinicopathological features and BRCA1 and BRCA2 mutation status in a prospective cohort of young women with breast cancer. Br J Cancer (2021). https://doi.org/10.1038/s41416-021-01597-2

Download citation

Search

Quick links