J Breast Cancer.  2014 Dec;17(4):301-307. 10.4048/jbc.2014.17.4.301.

Unique Features of Young Age Breast Cancer and Its Management

• Lee HB
• Han W

• KMID: 2176119
• DOI: http://doi.org/10.4048/jbc.2014.17.4.301

Abstract

Young age breast cancer (YABC) has unique clinical and biological features that are not seen in older patients. Breast tumor biology is more aggressive and is associated with an unfavorable prognosis in younger women. The diagnosis of breast cancer is often delayed, resulting in their initial presentation with more advanced disease. Together, these characteristics lead to a poorer prognosis in younger women than in older women. Young women who receive breast-conserving therapy have a higher rate of local recurrence. Therefore, it is important to secure sufficient resection margins and consider boost radiotherapy to prevent local treatment failure. Based on age alone, patients with YABC should be regarded as high-risk cases, and they should be treated with adjuvant chemotherapy. Special considerations regarding psychosocial factors and fertility should be taken into account for young patients. This review discusses the major considerations and principles concerning the management of patients with YABC.

Keyword

Age factors; Age of onset; Breast neoplasms; Disease management

MeSH Terms

Age Factors
Age of Onset
Biology
Breast Neoplasms*
Chemotherapy, Adjuvant
Diagnosis
Disease Management
Female
Fertility
Humans
Prognosis
Psychology
Radiotherapy
Recurrence
Treatment Failure

Reference

1. Stewart BW, Wild C. International Agency for Research on Cancer. World Health Organization. World Cancer Report 2014. Geneva: World Health Organization;2014.

2. American Cancer Society. Breast Cancer Facts & Figures 2011-2012. Atlanta: American Cancer Society;2011.

3. American Cancer Society. Breast Cancer Facts & Figures 2013-2014. Atlanta: American Cancer Society;2013.

4. Chung M, Chang HR, Bland KI, Wanebo HJ. Younger women with breast carcinoma have a poorer prognosis than older women. Cancer. 1996; 77:97–103.

5. Winchester DP. Breast cancer in young women. Surg Clin North Am. 1996; 76:279–287.

6. Ministry of Health and Welfare. Annual Report of Cancer Statistics in Korea in 2011. Goyang: Korea Central Cancer Registry;2012.

7. Han W, Kang SY. Korean Breast Cancer Society. 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; 119:193–200.

8. Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann 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; 24:2206–2223.

9. Walker RA, Lees E, Webb MB, Dearing SJ. Breast carcinomas occurring in young women (< 35 years) are different. Br J Cancer. 1996; 74:1796–1800.

10. Xiong Q, Valero V, Kau V, Kau SW, Taylor S, Smith TL, et al. Female patients with breast carcinoma age 30 years and younger have a poor prognosis: the M.D. Anderson Cancer Center experience. Cancer. 2001; 92:2523–2528.

11. Sidoni A, Cavaliere A, Bellezza G, Scheibel M, Bucciarelli E. Breast cancer in young women: clinicopathological features and biological specificity. Breast. 2003; 12:247–250.

12. Gonzalez-Angulo AM, Broglio K, Kau SW, Eralp Y, Erlichman J, Valero V, et al. Women age < or = 35 years with primary breast carcinoma: disease features at presentation. Cancer. 2005; 103:2466–2472.

13. Zabicki K, Colbert JA, Dominguez FJ, Gadd MA, Hughes KS, Jones JL, et al. Breast cancer diagnosis in women < or = 40 versus 50 to 60 years: increasing size and stage disparity compared with older women over time. Ann Surg Oncol. 2006; 13:1072–1077.

14. 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; 25:2360–2368.

15. Shak S, Baehner F, Stein M, Lewis S, Chen I, Yoshizawa C, et al. Quantitative gene expression analysis in a large cohort of estrogen receptor-positive breast cancers: characterization of the tumor profiles in younger patients (≤40 yrs) and in older patients (≥70 yrs). In : 33rd Annual San Antonio Breast Cancer Symposium; 2010. Abstract #P3-10-01.

16. Colleoni M, Rotmensz N, Robertson C, Orlando L, Viale G, Renne G, et al. Very young women (<35 years) with operable breast cancer: features of disease at presentation. Ann Oncol. 2002; 13:273–279.

17. Choi DH, Kim S, Rimm DL, Carter D, Haffty BG. Immunohistochemical biomarkers in patients with early-onset breast carcinoma by tissue microarray. Cancer J. 2005; 11:404–411.

18. Kim J, Han W, Park YH, Jung SY, Lee ES, Ro J, et al. Ki-67 level in hormone receptor positive breast cancer patients: a retrospective review of 9,061 Korean women. In : 2013 ASCO Annual Meeting; 2013. 31:Abstract #551.

19. 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; 26:3324–3330.

20. 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–e20.

21. Azim HA Jr, 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; 18:1341–1351.

22. Whittemore AS, Gong G, Itnyre J. Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer. Am J Hum Genet. 1997; 60:496–504.

23. Newman B, Mu H, Butler LM, Millikan RC, Moorman PG, King MC. Frequency of breast cancer attributable to BRCA1 in a population-based series of American women. JAMA. 1998; 279:915–921.

24. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, et al. Stratton MR. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst. 1999; 91:943–949.

25. Malone KE, Daling JR, Neal C, Suter NM, O’Brien C, Cushing-Haugen K, et al. Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer. 2000; 88:1393–1402.

26. Anglian Breast Cancer Study Group. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer. 2000; 83:1301–1308.

27. de Sanjosé S, Léoné M, Bérez V, Izquierdo A, Font R, Brunet JM, et al. Prevalence of BRCA1 and BRCA2 germline mutations in young breast cancer patients: a population-based study. Int J Cancer. 2003; 106:588–593.

28. Samphao S, Wheeler AJ, Rafferty E, Michaelson JS, Specht MC, Gadd MA, et al. Diagnosis of breast cancer in women age 40 and younger: delays in diagnosis result from underuse of genetic testing and breast imaging. Am J Surg. 2009; 198:538–543.

29. Robson M, Rajan P, Rosen PP, Gilewski T, Hirschaut Y, Pressman P, et al. BRCA-associated breast cancer: absence of a characteristic immunophenotype. Cancer Res. 1998; 58:1839–1842.

30. Robson M, Gilewski T, Haas B, Levin D, Borgen P, Rajan P, et al. BRCA-associated breast cancer in young women. J Clin Oncol. 1998; 16:1642–1649.

31. Warner E, Foulkes W, Goodwin P, Meschino W, Blondal J, Paterson C, et al. Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer. J Natl Cancer Inst. 1999; 91:1241–1247.

32. Ahn SH, Hwang UK, Kwak BS, Yoon HS, Ku BK, Kang HJ, et al. Prevalence of BRCA1 and BRCA2 mutations in Korean breast cancer patients. J Korean Med Sci. 2004; 19:269–274.

33. Barber MD, Jack W, Dixon JM. Diagnostic delay in breast cancer. Br J Surg. 2004; 91:49–53.

34. Friedman LC, Kalidas M, Elledge R, Dulay MF, Romero C, Chang J, et al. Medical and psychosocial predictors of delay in seeking medical consultation for breast symptoms in women in a public sector setting. J Behav Med. 2006; 29:327–334.

35. Jassem J, Ozmen V, Bacanu F, Drobniene M, Eglitis J, Lakshmaiah KC, et al. Delays in diagnosis and treatment of breast cancer: a multinational analysis. Eur J Public Health. 2014; 24:761–767.

36. Partridge AH, Hughes ME, Ottesen RA, Wong YN, Edge SB, Theriault RL, et al. The effect of age on delay in diagnosis and stage of breast cancer. Oncologist. 2012; 17:775–782.

37. Nixon AJ, Neuberg D, Hayes DF, Gelman R, Connolly JL, Schnitt S, et al. Relationship of patient age to pathologic features of the tumor and prognosis for patients with stage I or II breast cancer. J Clin Oncol. 1994; 12:888–894.

38. 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; 30:23–33.

39. Han W, Kim SW, Park IA, Kang D, Kim SW, Youn YK, et al. Young age: an independent risk factor for disease-free survival in women with operable breast cancer. BMC Cancer. 2004; 4:82.

40. Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Orlando L, Ghisini R, et al. Role of endocrine responsiveness and adjuvant therapy in very young women (below 35 years) with operable breast cancer and node negative disease. Ann Oncol. 2006; 17:1497–1503.

41. Goldhirsch A, Gelber RD, Yothers G, Gray RJ, Green S, Bryant J, et al. Adjuvant therapy for very young women with breast cancer: need for tailored treatments. J Natl Cancer Inst Monogr. 2001; (30):44–51.

42. Aebi S, Gelber S, Castiglione-Gertsch M, Gelber RD, Collins J, Thürlimann B, et al. Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer. Lancet. 2000; 355:1869–1874.

43. Fourquet A, Campana F, Zafrani B, Mosseri V, Vielh P, Durand JC, et al. Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-up. Int J Radiat Oncol Biol Phys. 1989; 17:719–725.

44. 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; 19:1688–1697.

45. Jobsen JJ, van der, Meerwaldt JH. The impact of age on local control in women with pT1 breast cancer treated with conservative surgery and radiation therapy. Eur J Cancer. 2001; 37:1820–1827.

46. Arriagada R, Lê MG, Contesso G, Guinebretière JM, Rochard F, Spielmann M. Predictive factors for local recurrence in 2006 patients with surgically resected small breast cancer. Ann Oncol. 2002; 13:1404–1413.

47. 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; 106:35–41.

48. Oh JL, Bonnen M, Outlaw ED, Schechter NR, Perkins GH, Strom EA, et al. The impact of young age on locoregional recurrence after doxorubicin-based breast conservation therapy in patients 40 years old or younger: How young is "young"? Int J Radiat Oncol Biol Phys. 2006; 65:1345–1352.

49. Bollet MA, Sigal-Zafrani B, Mazeau V, Savignoni A, de la Rochefordière 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; 82:272–280.

50. 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; 130:499–505.

51. 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; 100:688–693.

52. 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; 97:30–39.

53. Beadle BM, Woodward WA, Tucker SL, Outlaw ED, Allen PK, Oh JL, et al. Ten-year recurrence rates in young women with breast cancer by locoregional treatment approach. Int J Radiat Oncol Biol Phys. 2009; 73:734–744.

54. Quan ML, Osman F, McCready D, Fernandes K, Sutradhar R, Paszat L. Postmastectomy radiation and recurrence patterns in breast cancer patients younger than age 35 years: a population-based cohort. Ann Surg Oncol. 2014; 21:395–400.

55. Bedrosian I, Hu CY, Chang GJ. Population-based study of contralateral prophylactic mastectomy and survival outcomes of breast cancer patients. J Natl Cancer Inst. 2010; 102:401–409.

56. Breast cancer version 3. 2014. National Comprehensive Cancer Network. August 12th, 2014. http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

57. Howard-Anderson J, Ganz PA, Bower JE, Stanton AL. Quality of life, fertility concerns, and behavioral health outcomes in younger breast cancer survivors: a systematic review. J Natl Cancer Inst. 2012; 104:386–405.

58. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005; 365:1687–1717.

59. Kroman N, Jensen MB, Wohlfahrt J, Mouridsen HT, Andersen PK, Melbye M. Factors influencing the effect of age on prognosis in breast cancer: population based study. BMJ. 2000; 320:474–478.

60. De Laurentiis M, Cancello G, D’Agostino D, Giuliano M, Giordano A, Montagna E, et al. Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol. 2008; 26:44–53.

61. 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; 31:2692–2698.

62. 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; 381:805–816.

63. Minisini AM, Menis J, Valent F, Andreetta C, Alessi B, Pascoletti G, et al. Determinants of recovery from amenorrhea in premenopausal breast cancer patients receiving adjuvant chemotherapy in the taxane era. Anticancer Drugs. 2009; 20:503–507.

64. Regan MM, Pagani O, Fleming GF, Walley BA, Price KN, Rabaglio M, et al. Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials. Breast. 2013; 22:1094–1100.

65. Noh WC, Hur MH, Ahn SH, Jung Y, Lee SJ, Lee ES, et al. 32 ASTRRA study: a randomised phase III study for evaluating the role of the addition of ovarian function suppression (OFS) to tamoxifen in young women (<45 years) with hormone-sensitive breast cancer who remain in premenopause or regain menstruation after chemotherapy: a Korean Breast Cancer Study Group (KBCSG) trial. EJC Suppl. 2010; 8:67–68.

66. 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; 31:2500–2510.

67. Del Mastro L, Boni L, Michelotti A, Gamucci T, Olmeo N, Gori S, et al. Effect of the gonadotropin-releasing hormone analogue triptorelin on the occurrence of chemotherapy-induced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA. 2011; 306:269–276.

68. Del Mastro L, Ceppi M, Poggio F, Bighin C, Peccatori F, Demeestere I, et al. Gonadotropin-releasing hormone analogues for the prevention of chemotherapy-induced premature ovarian failure in cancer women: systematic review and meta-analysis of randomized trials. Cancer Treat Rev. 2014; 40:675–683.

69. Moore HC, Unger JM, Phillips KA, Boyle FM, Hitre E, Porter DJ, et al. 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). In : 2014 ASCO Annual Meeting; 2014. 32:Abstract #LBA505.

70. Zablotska LB, Neugut AI. Lung carcinoma after radiation therapy in women treated with lumpectomy or mastectomy for primary breast carcinoma. Cancer. 2003; 97:1404–1411.

71. Mulder RL, Kremer LC, Hudson MM, Bhatia S, Landier W, Levitt G, et al. Recommendations for breast cancer surveillance for female survivors of childhood, adolescent, and young adult cancer given chest radiation: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol. 2013; 14:e621–e629.

72. Kroenke CH, Rosner B, Chen WY, Kawachi I, Colditz GA, Holmes MD. Functional impact of breast cancer by age at diagnosis. J Clin Oncol. 2004; 22:1849–1856.

73. Northouse LL. Breast cancer in younger women: effects on interpersonal and family relations. J Natl Cancer Inst Monogr. 1994; (16):183–190.