Breast Cancer Research and Treatment

, Volume 147, Issue 3, pp 617–629 | Cite as

Breast cancer in young women: have the prognostic implications of breast cancer subtypes changed over time?

  • Wilson SheridanEmail author
  • Tyldesley Scott
  • Speers Caroline
  • Zheng Yvonne
  • Bernstein Vanessa
  • Voduc David
  • Gelmon Karen
  • Chia Stephen


We analyzed the impact of age according to subtype and compared outcomes for breast cancer (BC) patients across two time periods to determine whether the previously observed poor prognosis associated with BC in young women persists in the context of modern adjuvant therapies and relative to BC subtypes. Women aged <50 years (y) diagnosed with invasive BC between 1986–1992 and 2004–2007 were identified from British Columbia Cancer Agency’s Breast Cancer Outcomes Database and analyzed by age category (<40 and 40–49 years) and subtype. Subtypes were defined by immunohistochemistry. Relapse-free and overall survival (RFS and OS) were estimated using the Kaplan–Meier method. Multivariable analyses using Cox regression models were performed to adjust for prognostic variables. Age <40 was associated with inferior 5y-RFS for Luminal cases within both time cohorts (1986–1992: 65 vs. 77 %, P = 0.009, 2004–2007: 79 vs. 92 %, P = < 0.001). Inferior 5y-RFS was observed for those <40 with HER2-positive cancers in the 1986–1992, but not 2004–2007 cohort (49 vs. 66 %, P = 0.017, and 89 vs. 89 %, P = 0.879). No difference according to age was observed for triple-negative cancers in either time cohort (1986–1992: 60 vs. 63 %, P = 0.868, 2004–2007: 78 vs. 77 %, P = 0.933). 5y-RFS improved over time for all subgroups. OS for the Luminal subgroup improved for those 40–49 years but not <40 years. The effect of age varies with subtype. Age <40 years predicts inferior RFS and OS for Luminal BC in the modern era. Research efforts should target Luminal BC in young women for whom discrepancies in outcome persist.


Early-stage breast cancer Subtypes Luminal Young women Prognostic features 


Conflict of interest



  1. 1.
    El Saghir NS, Seoud M, Khalil MK et al (2006) Effects of young age at presentation on survival in breast cancer. BMC Cancer 6:194. doi: 10.1186/1471-2407-6-194 PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    de la Rochefordiere A, Asselain B, Campana F et al (1993) Age as prognostic factor in premenopausal breast carcinoma. Lancet 341:1039–1043PubMedCrossRefGoogle Scholar
  3. 3.
    Bharat A, Aft RL, Gao F et al (2009) Patient and tumor characteristics associated with increased mortality in young women (<or = 40 years) with breast cancer. J Surg Oncol 100:248–251. doi: 10.1002/jso.21268;10.1002/jso.21268 PubMedCrossRefGoogle Scholar
  4. 4.
    Anders CK, Johnson R, Litton J et al (2009) Breast cancer before age 40 years. Semin Oncol 36:237–249. doi: 10.1053/j.seminoncol.2009.03.001;10.1053/j.seminoncol.2009.03.001 PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Anders CK, Fan C, Parker JS et al (2011) Breast carcinomas arising at a young age: unique biology or a surrogate for aggressive intrinsic subtypes? J Clin Oncol 29:e18–20. doi: 10.1200/JCO.2010.28.9199;10.1200/JCO.2010.28.9199 PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Collins LC, Marotti JD, Gelber S et al (2012) Pathologic features and molecular phenotype by patient age in a large cohort of young women with breast cancer. Breast Cancer Res Treat 131:1061–1066. doi: 10.1007/s10549-011-1872-9;10.1007/s10549-011-1872-9 PubMedCrossRefGoogle Scholar
  7. 7.
    Colleoni M, Rotmensz N, Peruzzotti G et al (2006) Role of endocrine responsiveness and adjuvant therapy in very young women (below 35 years) with operable breast cancer and node negative disease. Ann Oncol 17:1497–1503. doi: 10.1093/annonc/mdl145 PubMedCrossRefGoogle Scholar
  8. 8.
    Smith BD, Jiang J, McLaughlin SS et al (2011) Improvement in breast cancer outcomes over time: are older women missing out? J Clin Oncol 29:4647–4653. doi: 10.1200/JCO.2011.35.8408 PubMedCrossRefGoogle Scholar
  9. 9.
    Brenner H, Francisci S, de Angelis R et al (2009) Long-term survival expectations of cancer patients in Europe in 2000–2002. Eur J Cancer 45:1028–1041. doi: 10.1016/j.ejca.2008.11.005 PubMedCrossRefGoogle Scholar
  10. 10.
    Verdecchia A, Guzzinati S, Francisci S et al (2009) Survival trends in European cancer patients diagnosed from 1988 to 1999. Eur J Cancer 45:1042–1066. doi: 10.1016/j.ejca.2008.11.029 PubMedCrossRefGoogle Scholar
  11. 11.
    Berry DA, Cronin KA, Plevritis SK et al (2005) Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med 353:1784–1792PubMedCrossRefGoogle Scholar
  12. 12.
    Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717. doi: 10.1016/S0140-6736(05)66544-0 CrossRefGoogle Scholar
  13. 13.
    Bria E, Nistico C, Cuppone F et al (2006) Benefit of taxanes as adjuvant chemotherapy for early breast cancer: pooled analysis of 15,500 patients. Cancer 106:2337–2344. doi: 10.1002/cncr.21886 PubMedCrossRefGoogle Scholar
  14. 14.
    Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672PubMedCrossRefGoogle Scholar
  15. 15.
    Carey LA, Perou CM, Livasy CA et al (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502. doi: 10.1001/jama.295.21.2492 PubMedCrossRefGoogle Scholar
  16. 16.
    Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98:10869–10874. doi: 10.1073/pnas.191367098 PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Sorlie T, Tibshirani R, Parker J et al (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA 100:8418–8423. doi: 10.1073/pnas.0932692100 PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Cancello G, Maisonneuve P, Rotmensz N et al (2010) Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer. Ann Oncol 21:1974–1981. doi: 10.1093/annonc/mdq072;10.1093/annonc/mdq072 PubMedCrossRefGoogle Scholar
  19. 19.
    Anders CK, Hsu DS, Broadwater G et al (2008) Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol 26:3324–3330. doi: 10.1200/JCO.2007.14.2471;10.1200/JCO.2007.14.2471 PubMedCrossRefGoogle Scholar
  20. 20.
    Bauer KR, Brown M, Cress RD et al (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109:1721–1728. doi: 10.1002/cncr.22618 PubMedCrossRefGoogle Scholar
  21. 21.
    Morrison DH, Rahardja D, King E et al (2012) Tumour biomarker expression relative to age and molecular subtypes of invasive breast cancer. Br J Cancer 107:382–387. doi: 10.1038/bjc.2012.219;10.1038/bjc.2012.219 PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Aebi S, Gelber S, Castiglione-Gertsch M et al (2000) Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer? Lancet 355:1869–1874PubMedCrossRefGoogle Scholar
  23. 23.
    Goldhirsch A, Gelber RD, Yothers G et al (2001) Adjuvant therapy for very young women with breast cancer: need for tailored treatments. J Natl Cancer Inst Monogr 30:44–51PubMedCrossRefGoogle Scholar
  24. 24.
    Kim EK, Noh WC, Han W et al (2011) Prognostic significance of young age (<35 years) by subtype based on ER, PR, and HER2 status in breast cancer: a nationwide registry-based study. World J Surg 35:1244–1253. doi: 10.1007/s00268-011-1071-1;10.1007/s00268-011-1071-1 PubMedCrossRefGoogle Scholar
  25. 25.
    Ahn SH, Son BH, Kim SW et al (2007) Poor outcome of hormone receptor-positive breast cancer at very young age is due to tamoxifen resistance: nationwide survival data in Korea—a report from the Korean Breast Cancer Society. J Clin Oncol 25:2360–2368. doi: 10.1200/JCO.2006.10.3754 PubMedCrossRefGoogle Scholar
  26. 26.
    Cheang MC, Voduc D, Bajdik C et al (2008) Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res 14:1368–1376. doi: 10.1158/1078-0432.CCR-07-1658;10.1158/1078-0432.CCR-07-1658 PubMedCrossRefGoogle Scholar
  27. 27.
    Partridge AH, Wang PS, Winer EP et al (2003) Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer. J Clin Oncol 21:602–606PubMedCrossRefGoogle Scholar
  28. 28.
    Hershman DL, Kushi LH, Shao T et al (2010) Early discontinuation and nonadherence to adjuvant hormonal therapy in a cohort of 8,769 early-stage breast cancer patients. J Clin Oncol 28:4120–4128. doi: 10.1200/JCO.2009.25.9655;10.1200/JCO.2009.25.9655 PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Hershman DL, Shao T, Kushi LH et al (2011) Early discontinuation and non-adherence to adjuvant hormonal therapy are associated with increased mortality in women with breast cancer. Breast Cancer Res Treat 126:529–537. doi: 10.1007/s10549-010-1132-4 PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Swain SM, Jeong JH, Geyer CE Jr et al (2010) Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 362:2053–2065. doi: 10.1056/NEJMoa0909638;10.1056/NEJMoa0909638 PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Parulekar WR, Day AG, Ottaway JA et al (2005) Incidence and prognostic impact of amenorrhea during adjuvant therapy in high-risk premenopausal breast cancer: analysis of a National Cancer Institute of Canada Clinical Trials Group Study–NCIC CTG MA.5. J Clin Oncol 23:6002–6008PubMedCrossRefGoogle Scholar
  32. 32.
    Pagani O, O’Neill A, Castiglione M et al (1998) Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: results of the International Breast Cancer Study Group (IBCSG) Trial VI. Eur J Cancer 34:632–640PubMedCrossRefGoogle Scholar
  33. 33.
    Petrek JA, Naughton MJ, Case LD et al (2006) Incidence, time course, and determinants of menstrual bleeding after breast cancer treatment: a prospective study. J Clin Oncol 24:1045–1051PubMedCrossRefGoogle Scholar
  34. 34.
    Walshe JM, Denduluri N, Swain SM (2006) Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol 24:5769–5779PubMedCrossRefGoogle Scholar
  35. 35.
    Pagani O, Regan MM, Walley BA et al (2014) Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. doi: 10.1056/NEJMoa1404037 PubMedGoogle Scholar
  36. 36.
    Berger NA (2014) Obesity and cancer pathogenesis. Ann N Y Acad Sci 1311:57–76. doi: 10.1111/nyas.12416 PubMedCrossRefGoogle Scholar
  37. 37.
    Pan H, Gray, Richard G on behalf of the Early Breast Cancer Trialists’ Collaborative Group (2014) Effect of obesity in premenopausal ER+ early breast cancer: EBCTCG data on 80,000 patients in 70 trials. JCO 32:abstract 503Google Scholar
  38. 38.
    Partridge AH, Gelber S, Piccart-Gebhart MJ et al (2013) Effect of age on breast cancer outcomes in women with human epidermal growth factor receptor 2-positive breast cancer: results from a herceptin adjuvant trial. J Clin Oncol 31:2692–2698. doi: 10.1200/JCO.2012.44.1956;10.1200/JCO.2012.44.1956 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Wilson Sheridan
    • 1
    Email author
  • Tyldesley Scott
    • 1
  • Speers Caroline
    • 1
  • Zheng Yvonne
    • 1
  • Bernstein Vanessa
    • 2
  • Voduc David
    • 1
  • Gelmon Karen
    • 1
  • Chia Stephen
    • 1
  1. 1.BC Cancer Agency, Vancouver Cancer CentreUniversity of British ColumbiaVancouverCanada
  2. 2.BC Cancer Agency, Vancouver Island Cancer CentreUniversity of British ColumbiaVictoriaCanada

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