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Breast Cancer Under Age 40: a Different Approach

  • Breast Cancer (P Neven, Section Editor)
  • Published:
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Opinion statement

Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90 % of young patients with BC are symptomatic. Women <40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age <40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC <40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2 % in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient’s comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in presence of visceral metastases, unless there is concern or proof of endocrine resistance or there is a need for rapid disease response and/or symptom control. Recommendations for chemotherapy (CT) should not differ from those for older patients with the same characteristics of the metastatic disease and its extent. Young age by itself should not be an indication to prescribe more intensive and combination CT regimens over the sequential use of monotherapy. Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) represent an important group of promising drugs in managing patients with breast cancer susceptibility gene (BRCA)-1- or BRCA-2-associated BC. Specific age-related side effects of systemic treatment (e.g., menopausal symptoms, change in body image, bone morbidity, cognitive function impairment, fertility damage, sexual dysfunction) and the social impact of diagnosis and treatment (job discrimination, taking care for children) should also be carefully addressed when planning systemic long-lasting therapy, such as endocrine therapy. Survivorship concerns for young women are different compared to older women, including issues of fertility, preservation, and pregnancy.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. American Cancer Society. Breast cancer facts & figures 2011–2012. Atlanta: American Cancer Society, Inc.; 2012.

    Google Scholar 

  2. Freedman RA, Partridge AH. Management of breast cancer in very young women. Breast. 2013;22 Suppl 2:S176–9. This article highlights the importance of special considerations for young patients when deciding/selecting adjuvant treatment options.

    Article  PubMed  Google Scholar 

  3. Cardoso F, Loibl S, Pagani O, Graziottin A, Panizza P, Martincich L, et al. The European Society of Breast Cancer Specialists recommendations for the management of young women with breast cancer. Eur J Cancer. 2012;48(18):3355–77.

    Article  PubMed  Google Scholar 

  4. Partridge AH, Pagani O, Abulkhair O, Aebi S, Amant F, Azim Jr HA, et al. First international consensus guidelines for breast cancer in young women (BCY1). Breast. 2014;23(3):209–20.

    Article  PubMed  Google Scholar 

  5. Sardanelli F, Boetes C, Borisch B, Decker T, Federico M, Gilbert FJ, et al. Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. Eur J Cancer. 2010;46(8):1296–316.

    Article  PubMed  Google Scholar 

  6. Yamamoto S, Chishima T, Mastubara Y, Adachi S, Harada F, Toda Y, et al. Variability in measuring the ki-67 labeling index in patients with breast cancer. Clin Breast Cancer. 2015;15(1):e35–9.

    Article  PubMed  Google Scholar 

  7. Mann RM, Loo CE, Wobbes T, Bult P, Barentsz JO, Gilhuijs KG, et al. The impact of preoperative breast MRI on the re-excision rate in invasive lobular carcinoma of the breast. Breast Cancer Res Treat. 2010;119(2):415–22.

    Article  CAS  PubMed  Google Scholar 

  8. Copson E, Eccles B, Maishman T, Gerty S, Stanton L, Cutress RI, et al. Prospective observational study of breast cancer treatment outcomes for UK women aged 18–40 years at diagnosis: the POSH study. J Natl Cancer Inst. 2013;105(13):978–88.

    Article  CAS  PubMed  Google Scholar 

  9. 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(3):1061–6.

    Article  CAS  PubMed  Google Scholar 

  10. Gnerlich JL, Deshpande AD, Jeffe DB, Sweet A, White N, Margenthaler JA. Elevated breast cancer mortality in women younger than age 40 years compared with older women is attributed to poorer survival in early-stage disease. J Am Coll Surg. 2009;208(3):341–7.

    Article  PubMed Central  PubMed  Google Scholar 

  11. 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(2):R55.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Acevedo C, Amaya C, Lopez-Guerra JL. Rare breast tumors: review of the literature. Rep Pract Oncol Radiother. 2014;19(4):267–74.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Bayraktar S, Amendola L, Gutierrez-Barrera AM, Hashmi SS, Amos C, Gambello M, et al. Clinicopathologic characteristics of breast cancer in BRCA-carriers and non-carriers in women 35 years of age or less. Breast. 2014.

  14. Wolff AC, Hammond ME, Hicks DG, Dowsett M, McShane LM, Allison KH, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol. 2013;31(31):3997–4013.

    Article  PubMed  Google Scholar 

  15. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013;24(9):2206–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490(7418):61–70.

  17. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest. 2011;121(7):2750–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Azim Jr 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(5):1341–51. This reference explains the complexity of BC in young patients and stresses independency of this complexity among different BC intrinsic subtypes. Furthermore, it discusses the importance of well designed prospective clinical trials in this subgroup population of BC patients—targeting specific signal pathways.

    Article  CAS  PubMed  Google Scholar 

  19. van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009.

    Article  PubMed  Google Scholar 

  20. Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817–26.

    Article  CAS  PubMed  Google Scholar 

  21. Anders CK, Acharya CR, Hsu DS, Broadwater G, Garman K, Foekens JA, et al. Age-specific differences in oncogenic pathway deregulation seen in human breast tumors. PLoS ONE. 2008;3(1):e1373.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. 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.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Criscitiello C, Azim Jr HA, Schouten PC, Linn SC, Sotiriou C. Understanding the biology of triple-negative breast cancer. Ann Oncol. 2012;23 Suppl 6:vi13–8.

    Article  PubMed  Google Scholar 

  24. Anders CK, Johnson R, Litton J, Phillips M, Bleyer A. Breast cancer before age 40 years. Semin Oncol. 2009;36(3):237–49.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Bharat A, Aft RL, Gao F, Margenthaler JA. Patient and tumor characteristics associated with increased mortality in young women (< or =40 years) with breast cancer. J Surg Oncol. 2009;100(3):248–51.

    Article  PubMed  Google Scholar 

  26. Anders CK, Hsu DS, Broadwater G, Acharya CR, Foekens JA, Zhang Y, et al. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J Clin Oncol. 2008;26(20):3324–30.

    Article  PubMed  Google Scholar 

  27. Fredholm H, Eaker S, Frisell J, Holmberg L, Fredriksson I, Lindman H. Breast cancer in young women: poor survival despite intensive treatment. PLoS ONE. 2009;4(11):e7695.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Sheridan W, Scott T, Caroline S, Yvonne Z, Vanessa B, David V, et al. Breast cancer in young women: have the prognostic implications of breast cancer subtypes changed over time? Breast Cancer Res Treat. 2014;147(3):617–29.

    Article  PubMed  Google Scholar 

  29. Partridge AH, Gelber S, Piccart-Gebhart MJ, Focant F, Scullion M, Holmes E, et al. 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. 2013;31(21):2692–8.

    Article  CAS  PubMed  Google Scholar 

  30. Cardoso F, Costa A, Norton L, Cameron D, Cufer T, Fallowfield L, et al. 1st international consensus guidelines for advanced breast cancer (ABC 1). Breast. 2012;21(3):242–52.

    Article  CAS  PubMed  Google Scholar 

  31. Cardoso F, Costa A, Norton L, Senkus E, Aapro M, Andre F, et al. ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Breast. 2014;23(5):489–502.

    Article  CAS  PubMed  Google Scholar 

  32. Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med. 2002;347(16):1227–32.

    Article  PubMed  Google Scholar 

  33. Kroman N, Holtveg H, Wohlfahrt J, Jensen MB, Mouridsen HT, Blichert-Toft M, et al. Effect of breast-conserving therapy versus radical mastectomy on prognosis for young women with breast carcinoma. Cancer. 2004;100(4):688–93.

    Article  PubMed  Google Scholar 

  34. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, 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. 2011;378(9804):1707–16.

    Article  CAS  PubMed  Google Scholar 

  35. Donker M, Litiere S, Werutsky G, Julien JP, Fentiman IS, Agresti R, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma in situ: 15-year recurrence rates and outcome after a recurrence, from the EORTC 10853 randomized phase III trial. J Clin Oncol. 2013;31(32):4054–9.

    Article  PubMed  Google Scholar 

  36. van Laar C, van der Sangen MJ, Poortmans PM, Nieuwenhuijzen GA, Roukema JA, Roumen RM, et al. Local recurrence following breast-conserving treatment in women aged 40 years or younger: trends in risk and the impact on prognosis in a population-based cohort of 1143 patients. Eur J Cancer. 2013;49(15):3093–101.

    Article  PubMed  Google Scholar 

  37. Rosenberg SM, Tamimi RM, Gelber S, Ruddy KJ, Kereakoglow S, Borges VF, et al. Body image in recently diagnosed young women with early breast cancer. Psychooncology. 2013;22(8):1849–55.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Immink JM, Putter H, Bartelink H, Cardoso JS, Cardoso MJ, van der Hulst-Vijgen MH, et al. Long-term cosmetic changes after breast-conserving treatment of patients with stage I-II breast cancer and included in the EORTC ‘boost versus no boost’ trial. Ann Oncol. 2012;23(10):2591–8.

    Article  CAS  PubMed  Google Scholar 

  39. de Alcantara FP, Capko D, Barry JM, Morrow M, Pusic A, Sacchini VS. Nipple-sparing mastectomy for breast cancer and risk-reducing surgery: the Memorial Sloan-Kettering Cancer Center experience. Ann Surg Oncol. 2011;18(11):3117–22.

    Article  Google Scholar 

  40. Mamounas EP, Anderson SJ, Dignam JJ, Bear HD, Julian TB, Geyer Jr CE, 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. 2012;30(32):3960–6.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Adkisson CD, Vallow LA, Kowalchik K, McNeil R, Hines S, Deperi E, et al. Patient age and preoperative breast MRI in women with breast cancer: biopsy and surgical implications. Ann Surg Oncol. 2011;18(6):1678–83.

    Article  PubMed  Google Scholar 

  42. Pierce LJ, Phillips KA, Griffith KA, Buys S, Gaffney DK, Moran MS, et al. Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat. 2010;121(2):389–98.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Valachis A, Nearchou AD, Lind P. Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2014;144(3):443–55.

    Article  CAS  PubMed  Google Scholar 

  44. Metcalfe K, Lynch HT, Ghadirian P, Tung N, Kim-Sing C, Olopade OI, et al. Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2011;127(1):287–96.

    Article  CAS  PubMed  Google Scholar 

  45. Heemskerk-Gerritsen B, Hooning M, van Asperen CJ, et al. Efficacy of risk-reducing mastectomy (RRM) on overall survival (OS) in BRCA1/2-associated breast cancer (BC) patients. J Clin Oncol (Meeting Abstracts). 2013;(Meeting Abstracts) 31(15 suppl):1502.

  46. Lokich E, Stuckey A, Raker C, Wilbur JS, Laprise J, Gass J. Preoperative genetic testing affects surgical decision making in breast cancer patients. Gynecol Oncol. 2014;134(2):326–30.

    Article  PubMed  Google Scholar 

  47. Niemeyer M, Paepke S, Schmid R, Plattner B, Muller D, Kiechle M. Extended indications for nipple-sparing mastectomy. Breast J. 2011;17(3):296–9.

    Article  PubMed  Google Scholar 

  48. Elkhuizen PH, van de Vijver MJ, Hermans J, Zonderland HM, van de Velde CJ, Leer JW. Local recurrence after breast-conserving therapy for invasive breast cancer: high incidence in young patients and association with poor survival. Int J Radiat Oncol Biol Phys. 1998;40(4):859–67.

    Article  CAS  PubMed  Google Scholar 

  49. Han W, Kang SY. Relationship between age at diagnosis and outcome of premenopausal breast cancer: age less than 35 years is a reasonable cut-off for defining young age-onset breast cancer. Breast Cancer Res Treat. 2010;119(1):193–200.

    Article  PubMed  Google Scholar 

  50. O’Rourke MT, Ellison PT. Age and prognosis in premenopausal breast cancer. Lancet. 1993;342(8862):60.

    Article  PubMed  Google Scholar 

  51. Ahn SH, Son BH, Kim SW, Kim SI, Jeong J, Ko SS, et al. 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. 2007;25(17):2360–8.

    Article  PubMed  Google Scholar 

  52. Bollet MA, Sigal-Zafrani B, Mazeau V, Savignoni A, de la Rochefordiere A, Vincent-Salomon A, et al. Age remains the first prognostic factor for loco-regional breast cancer recurrence in young (<40 years) women treated with breast conserving surgery first. Radiother Oncol. 2007;82(3):272–80.

    Article  PubMed  Google Scholar 

  53. Kim HJ, Han W, Yi OV, Shin HC, Ahn SK, Koh BS, et al. Young age is associated with ipsilateral breast tumor recurrence after breast conserving surgery and radiation therapy in patients with HER2-positive/ER-negative subtype. Breast Cancer Res Treat. 2011;130(2):499–505.

    Article  PubMed  Google Scholar 

  54. Bartelink H, Horiot JC, Poortmans P, Struikmans H, Van den Bogaert W, Barillot I, et al. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med. 2001;345(19):1378–87.

    Article  CAS  PubMed  Google Scholar 

  55. Botteri E, Bagnardi V, Rotmensz N, Gentilini O, Disalvatore D, Bazolli B, et al. Analysis of local and regional recurrences in breast cancer after conservative surgery. Ann Oncol. 2010;21(4):723–8.

    Article  CAS  PubMed  Google Scholar 

  56. Komoike Y, Akiyama F, Iino Y, Ikeda T, Akashi-Tanaka S, Ohsumi S, et al. Ipsilateral breast tumor recurrence (IBTR) after breast-conserving treatment for early breast cancer: risk factors and impact on distant metastases. Cancer. 2006;106(1):35–41.

    Article  PubMed  Google Scholar 

  57. Zhou P, Gautam S, Recht A. Factors affecting outcome for young women with early stage invasive breast cancer treated with breast-conserving therapy. Breast Cancer Res Treat. 2007;101(1):51–7.

    Article  CAS  PubMed  Google Scholar 

  58. Albert JM, Gonzalez-Angulo AM, Guray M, Sahin A, Strom EA, Tereffe W, et al. Estrogen/progesterone receptor negativity and HER2 positivity predict locoregional recurrence in patients with T1a, bN0 breast cancer. Int J Radiat Oncol Biol Phys. 2010;77(5):1296–302.

    Article  CAS  PubMed  Google Scholar 

  59. 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(1):e18–20.

    Article  PubMed Central  PubMed  Google Scholar 

  60. Antonini N, Jones H, Horiot JC, Poortmans P, Struikmans H, Van den Bogaert W, et al. Effect of age and radiation dose on local control after breast conserving treatment: EORTC trial 22881-10882. Radiother Oncol. 2007;82(3):265–71.

    Article  PubMed  Google Scholar 

  61. Coulombe G, Tyldesley S, Speers C, Paltiel C, Aquino-Parsons C, Bernstein V, et al. Is mastectomy superior to breast-conserving treatment for young women? Int J Radiat Oncol Biol Phys. 2007;67(5):1282–90.

    Article  PubMed  Google Scholar 

  62. Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, et al. Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol. 2008;26(14):2373–8.

    Article  PubMed  Google Scholar 

  63. Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010;28(10):1684–91.

    Article  PubMed  Google Scholar 

  64. Fowble BL, Schultz DJ, Overmoyer B, Solin LJ, Fox K, Jardines L, et al. The influence of young age on outcome in early stage breast cancer. Int J Radiat Oncol Biol Phys. 1994;30(1):23–33.

    Article  CAS  PubMed  Google Scholar 

  65. Jones HA, Antonini N, Hart AA, Peterse JL, Horiot JC, Collin F, et al. Impact of pathological characteristics on local relapse after breast-conserving therapy: a subgroup analysis of the EORTC boost versus no boost trial. J Clin Oncol. 2009;27(30):4939–47.

    Article  PubMed Central  PubMed  Google Scholar 

  66. Voogd AC, Nielsen M, Peterse JL, Blichert-Toft M, Bartelink H, Overgaard M, et al. Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: pooled results of two large European randomized trials. J Clin Oncol. 2001;19(6):1688–97.

    CAS  PubMed  Google Scholar 

  67. Bartelink H, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol. 2007;25(22):3259–65.

    Article  PubMed  Google Scholar 

  68. Neuschatz AC, DiPetrillo T, Safaii H, Price LL, Schmidt-Ullrich RK, Wazer DE. Long-term follow-up of a prospective policy of margin-directed radiation dose escalation in breast-conserving therapy. Cancer. 2003;97(1):30–9.

    Article  PubMed  Google Scholar 

  69. Letourneau JM, Melisko ME, Cedars MI, Rosen MP. A changing perspective: improving access to fertility preservation. Nat Rev Clin Oncol. 2011;8(1):56–60. An important issue about fertility in young BC patients.

    Article  PubMed Central  PubMed  Google Scholar 

  70. Ribeiro J, Sousa B, Cardoso F. Optimal approach in early breast cancer: adjuvant and neoadjuvant treatment. EJC Supplements II 2013; 3–22. 2013.

  71. Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, Stemmer SM. Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst. 2010;102(24):1845–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Huober J, von Minckwitz G, Denkert C, Tesch H, Weiss E, Zahm DM, et al. Effect of neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study. Breast Cancer Res Treat. 2010;124(1):133–40.

    Article  CAS  PubMed  Google Scholar 

  73. Anders CK, Zagar TM, Carey LA. The management of early-stage and metastatic triple-negative breast cancer: a review. Hematol Oncol Clin N Am. 2013;27(4):737–49. 4.

    Article  Google Scholar 

  74. Petrelli F, Coinu A, Borgonovo K, Cabiddu M, Ghilardi M, Lonati V, et al. The value of platinum agents as neoadjuvant chemotherapy in triple-negative breast cancers: a systematic review and meta-analysis. Breast Cancer Res Treat. 2014;144(2):223–32. An important meta-analysis of the value of platinum compound in the management of triple-negative BCs.

    Article  CAS  PubMed  Google Scholar 

  75. von Minckwitz G, Schneeweiss A, Loibl S, Salat C, Denkert C, Rezai M, et al. Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol. 2014;15(7):747–56.

    Article  CAS  Google Scholar 

  76. Paluch-Shimon S, Friedman E, Berger R, et al. Does pathologic complete response predict for outcome in BRCA mutation carriers with triple-negative breast cancer? J Clin Oncol. 2014;32:5s,(suppl; abstr 1023). Important issue of predictive value of pCR in BRCA-positive triple-negative BC patients.

  77. Christinat A, Di Lascio S, Pagani O. Hormonal therapies in young breast cancer patients: when, what and for how long? J Thorac Dis. 2013;5 Suppl 1:S36–46. Extensive discussion of many endocrine treatment options for young BC patients.

    PubMed Central  PubMed  Google Scholar 

  78. Masuda N, Sagara Y, Kinoshita T, Iwata H, Nakamura S, Yanagita Y, et al. Neoadjuvant anastrozole versus tamoxifen in patients receiving goserelin for premenopausal breast cancer (STAGE): a double-blind, randomised phase 3 trial. Lancet Oncol. 2012;13(4):345–52.

    Article  CAS  PubMed  Google Scholar 

  79. Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, 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. 2011;378(9793):771–84.

    Article  CAS  PubMed  Google Scholar 

  80. Davies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013;381(9869):805–16. An important large clinical trial evaluating the role of TAM 10 vs 5 years with special attention to benefit that was the biggest in the year 10 and beyond – carry over effect.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Gray RG, Rea D, Handley K, et al. aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol. 2013;31(suppl):abstr 5.

    Google Scholar 

  82. Azim HA, Saadeldeen A. Commentary on “aTTom”: long-term effects of continuing adjuvant Tamoxifen to 10 years. Chin Clin Oncol. 2014;3(1):7.

    PubMed  Google Scholar 

  83. Cuzick J, Ambroisine L, Davidson N, Jakesz R, Kaufmann M, Regan M, et al. Use of luteinising-hormone-releasing hormone agonists as adjuvant treatment in premenopausal patients with hormone-receptor-positive breast cancer: a meta-analysis of individual patient data from randomised adjuvant trials. Lancet. 2007;369(9574):1711–23.

    Article  CAS  PubMed  Google Scholar 

  84. Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436–46.

    Article  CAS  PubMed  Google Scholar 

  85. Olivia Pagani M, on behalf of the TEXT and SOFT Investigators and International Breast Cancer Study Group (IBCSG). Randomized comparison of adjuvant aromatase inhibitor exemestane plus ovarian function suppression vs tamoxifen plus ovarian function suppression in premenopausal women with hormone receptor positive early breast cancer: joint analysis of IBCSG TEXT and SOFT. J Clin Oncol. 2014;ASCO 2014. Abstract LBA1. The role of AIs in premenopausal patients with early BC.

  86. Vidal LBAI, Rizel S, et al. Bisphosphonates in the adjuvant setting of breast cancer therapy: effect on survival—a systematic review and meta-analysis. J Clin Oncol. 2012;30:abstr 548. The role of bisphosphonates in adjuvant setting as »preventive« agents in EBC patients. Young (premenopausal) patients receiving bisphosphonates in adjuvant setting have higher rate of non-skeletal distant events.

    Article  Google Scholar 

  87. Coleman RE, Marshall H, Cameron D, Dodwell D, Burkinshaw R, Keane M, et al. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med. 2011;365(15):1396–405.

    Article  CAS  PubMed  Google Scholar 

  88. Azim HA, Kamal NS, Malak RA. Bisphosphonates in the adjuvant treatment of young women with breast cancer: the estrogen rich is a poor candidate! J Thorac Dis. 2013;5 Suppl 1:S27–35.

    PubMed Central  PubMed  Google Scholar 

  89. Gnant M, Mlineritsch B, Luschin-Ebengreuth G, et al. Long-term follow-up in ABCSG-12: significantly improved overall survival with adjuvant zoledronic acid in premenopausal patients with endocrine-receptor-positive early breast cancer. Cancer Res. 2011;71:S1–2.

    Article  Google Scholar 

  90. Robertson FM, Bondy M, Yang W, Yamauchi H, Wiggins S, Kamrudin S, et al. Inflammatory breast cancer: the disease, the biology, the treatment. CA Cancer J Clin. 2010;60(6):351–75.

    Article  PubMed  Google Scholar 

  91. Cardoso F, Costa A, Norton L, Senkus E, Aapro M, Andre F, et al. ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2) dagger. Ann Oncol. 2014;25(10):1871–88.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Bartsch R, Bago-Horvath Z, Berghoff A, DeVries C, Pluschnig U, Dubsky P, et al. Ovarian function suppression and fulvestrant as endocrine therapy in premenopausal women with metastatic breast cancer. Eur J Cancer. 2012;48(13):1932–8.

    Article  CAS  PubMed  Google Scholar 

  93. Isakoff SJ. Triple-negative breast cancer: role of specific chemotherapy agents. Cancer J. 2010;16(1):53–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Tutt A, Ellis P, Kilburn L, et al. The TNT trial: a randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/07/012). Program and abstracts of the 2014 San Antonio Breast Cancer Symposium December 9–13, 2014; San Antonio, Texas Abstract S3-01. 2014.

  95. Aebi S, Gelber S, Anderson SJ, Lang I, Robidoux A, Martin M, et al. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol. 2014;15(2):156–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet. 2010;376(9737):235–44.

    Article  CAS  PubMed  Google Scholar 

  97. Isakoff SJ, Overmoyer B, Tung NM, Gelman RS, Giranda VL, Bernhard KM, et al. A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer. J Clin Oncol. 2010;28:15s, 2010(suppl; abstr 1019).

  98. EMBRACA study. https://clinicaltrials.gov/ct2/show/NCT01945775

  99. Study B. https://clinicaltrials.gov/ct2/show/NCT01905592?term=Breast+cancer+AND+PARP+AND+BRCA&phase=2&rank=3.

  100. Senkus E, Kyriakides S, Penault-Llorca F, Poortmans P, Thompson A, Zackrisson S, et al. Primary breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi7–23.

    Article  PubMed  Google Scholar 

  101. Gorechlad JW, McCabe EB, Higgins JH, Likosky DS, Lewis PJ, Rosenkranz KM, et al. Screening for recurrences in patients treated with breast-conserving surgery: is there a role for MRI? Ann Surg Oncol. 2008;15(6):1703–9.

    Article  PubMed  Google Scholar 

  102. Kontos M, Allen DS, Agbaje OF, Hamed H, Fentiman IS. Factors influencing loco-regional relapse in older breast cancer patients treated with tumour resection and tamoxifen. Eur J Surg Oncol. 2011;37(12):1051–8.

    Article  CAS  PubMed  Google Scholar 

  103. Kim HJ, Kwak JY, Choi JW, Bae JH, Shin KM, Lee HJ, et al. Impact of US surveillance on detection of clinically occult locoregional recurrence after mastectomy for breast cancer. Ann Surg Oncol. 2010;17(10):2670–6.

    Article  PubMed  Google Scholar 

  104. Kim J, Kim M, Lee JH, Lee H, Lee SK, Bae SY, et al. Ovarian function preservation with GnRH agonist in young breast cancer patients: does it impede the effect of adjuvant chemotherapy? Breast. 2014;23(5):670–5.

    Article  PubMed  Google Scholar 

  105. Berkowitz GS, Skovron ML, Lapinski RH, Berkowitz RL. Delayed childbearing and the outcome of pregnancy. N Engl J Med. 1990;322(10):659–64.

    Article  CAS  PubMed  Google Scholar 

  106. Cooke A, Mills TA, Lavender T. ‘Informed and uninformed decision making’—women’s reasoning, experiences and perceptions with regard to advanced maternal age and delayed childbearing: a meta-synthesis. Int J Nurs Stud. 2010;47(10):1317–29.

    Article  PubMed  Google Scholar 

  107. Lange S, Tait D, Matthews M. Oncofertility: an emerging discipline in obstetrics and gynecology. Obstet Gynecol Surv. 2013;68(8):582–93.

    Article  PubMed  Google Scholar 

  108. Meirow D, Dor J, Kaufman B, Shrim A, Rabinovici J, Schiff E, et al. Cortical fibrosis and blood-vessels damage in human ovaries exposed to chemotherapy. Potential mechanisms of ovarian injury. Hum Reprod. 2007;22(6):1626–33.

    Article  CAS  PubMed  Google Scholar 

  109. Christinat A, Pagani O. Fertility after breast cancer. Maturitas. 2012;73(3):191–6.

    Article  PubMed  Google Scholar 

  110. Rodriguez-Wallberg KA, Oktay K. Options on fertility preservation in female cancer patients. Cancer Treat Rev. 2012;38(5):354–61.

    Article  PubMed  Google Scholar 

  111. Ronn R, Holzer HE. Oncofertility in Canada: the impact of cancer on fertility. Curr Oncol. 2013;20(4):e338–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  112. Walshe JM, Denduluri N, Swain SM. Amenorrhea in premenopausal women after adjuvant chemotherapy for breast cancer. J Clin Oncol. 2006;24(36):5769–79.

    Article  CAS  PubMed  Google Scholar 

  113. Casey PM, Faubion SS, MacLaughlin KL, Long ME, Pruthi S. Caring for the breast cancer survivor’s health and well-being. World J Clin Oncol. 2014;5(4):693–704.

    Article  PubMed Central  PubMed  Google Scholar 

  114. Hatcher Trussel J, Nelson AL, Cates Jr W, Kowal D, Policar MS, editors. Contraceptive technology (20th revised ed.). New York: Ardent Media; 2011.

    Google Scholar 

  115. Dinger J, Bardenheuer K, Minh TD. Levonorgestrel-releasing and copper intrauterine devices and the risk of breast cancer. Contraception. 2011;83(3):211–7.

    Article  CAS  PubMed  Google Scholar 

  116. Loren AW, Mangu PB, Beck LN, Brennan L, Magdalinski AJ, Partridge AH, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31(19):2500–10.

    Article  PubMed  Google Scholar 

  117. Friedler S, Koc O, Gidoni Y, Raziel A, Ron-El R. Ovarian response to stimulation for fertility preservation in women with malignant disease: a systematic review and meta-analysis. Fertil Steril. 2012;97(1):125–33.

    Article  PubMed  Google Scholar 

  118. Moore H. Phase III trial (Prevention of Early Menopause Study [POEMS]-SWOG S0230) of LHRH analog during chemotherapy (CT) to reduce ovarian failure in early-stage, hormone receptor-negative breast cancer: an international Intergroup trial of SWOG, IBCSG, ECOG, and CALGB (Alliance). J Clin Oncol 32:5s, 2014(suppl; abstr LBA505). 2014.

  119. Gerber B, von Minckwitz G, Stehle H, Reimer T, Felberbaum R, Maass N, et al. Effect of luteinizing hormone-releasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study. J Clin Oncol. 2011;29(17):2334–41.

    Article  CAS  PubMed  Google Scholar 

  120. Peccatori FA, Azim HA, Azim Jr HA, Orecchia R, Hoekstra HJ, Pavlidis N, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24 Suppl 6:vi160–70.

    Article  PubMed  Google Scholar 

  121. Rosen A. Third-party reproduction and adoption in cancer patients. J Natl Cancer Inst Monogr. 2005;34:91–3.

    Article  PubMed  Google Scholar 

  122. Pagani O, Azim Jr H. Pregnancy after breast cancer: myths and facts. Breast Care (Basel). 2012;7(3):210–4. An important discussion on pregnancy after BC diagnosis and treatment.

    Article  Google Scholar 

  123. Azim Jr HA, Kroman N, Paesmans M, Gelber S, Rotmensz N, Ameye L, et al. Prognostic impact of pregnancy after breast cancer according to estrogen receptor status: a multicenter retrospective study. J Clin Oncol. 2013;31(1):73–9.

    Article  PubMed Central  PubMed  Google Scholar 

  124. Azim Jr HA, Santoro L, Pavlidis N, Gelber S, Kroman N, Azim H, et al. Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies. Eur J Cancer. 2011;47(1):74–83.

    Article  PubMed  Google Scholar 

  125. Helewa M, Levesque P, Provencher D, Lea RH, Rosolowich V, Shapiro HM. Breast cancer, pregnancy, and breastfeeding. J Obstet Gynaecol Can. 2002;24(2):164–80. quiz 81-4.

    PubMed  Google Scholar 

  126. Azim Jr HA, Metzger-Filho O, de Azambuja E, Loibl S, Focant F, Gresko E, et al. Pregnancy occurring during or following adjuvant trastuzumab in patients enrolled in the HERA trial (BIG 01-01). Breast Cancer Res Treat. 2012;133(1):387–91.

    Article  CAS  PubMed  Google Scholar 

  127. Valentini A, Lubinski J, Byrski T, Ghadirian P, Moller P, Lynch HT, et al. The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation. Breast Cancer Res Treat. 2013;142(1):177–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Milne RL, Osorio A, Ramon y Cajal T, Baiget M, Lasa A, Diaz-Rubio E, et al. Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat. 2010;119(1):221–32.

    Article  CAS  PubMed  Google Scholar 

  129. Cullinane CA, Lubinski J, Neuhausen SL, Ghadirian P, Lynch HT, Isaacs C, et al. Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers. Int J Cancer. 2005;117(6):988–91.

    Article  CAS  PubMed  Google Scholar 

  130. Friebel TM, Domchek SM, Rebbeck TR. Modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: systematic review and meta-analysis. J Natl Cancer Inst. 2014;106(6):dju091.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Conflict of Interest

Fatima Cardoso is a consultant to Astellas, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, GSK, Merck-Sharp, Merus, Novartis, Pfizer, Roche, and Sanofi.

D Ribnikar, JM Ribeiro, D Pinto, B Sousa, AC Pinto, E Gomes, EC Moser, and MJ Cardoso declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Medical Oncology Department, Institute of Oncology Ljubljana, Ljubljana, Slovenia

    D. Ribnikar MD

  2. Breast Unit, Champalimaud Clinical Center, Av. De Brasília, s/n, 1400-038, Lisbon, Portugal

    J. M. Ribeiro MD, D. Pinto MD, B. Sousa MD, A. C. Pinto MD, E. Gomes MD, E. C. Moser MD, PhD, M. J. Cardoso MD & F. Cardoso MD, PhD

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Correspondence to F. Cardoso MD, PhD.

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This article is part of the Topical Collection on Breast Cancer

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Ribnikar, D., Ribeiro, J.M., Pinto, D. et al. Breast Cancer Under Age 40: a Different Approach. Curr. Treat. Options in Oncol. 16, 16 (2015). https://doi.org/10.1007/s11864-015-0334-8

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