Breast Cancer Research and Treatment

, Volume 165, Issue 2, pp 311–320 | Cite as

Survival improvement in hormone-responsive young breast cancer patients with endocrine therapy

  • Tae In Yoon
  • Ui-Kang Hwang
  • Eui Tae Kim
  • SaeByul Lee
  • Guiyun Sohn
  • Beom Seok Ko
  • Jong Won Lee
  • Byung Ho Son
  • Seonok Kim
  • Sei Hyun Ahn
  • Hee Jeong Kim
Clinical trial

Abstract

Purpose

We investigated the oncologic outcomes by intrinsic subtype and age in young breast cancer patients and whether survival differences were related to treatment changes over time.

Methods

A retrospective analysis was performed on 9633 invasive breast cancer patients treated at Asan Medical Center from January 1989 to December 2008. We also enrolled a matched cohort adjusting for tumor size, lymph node metastasis, subtypes, and tumor grade. Patients aged <35 years were included in the younger group (n = 602) and those aged ≥35 years were included in the older group (n = 3009).

Results

The younger patients showed a significantly higher T stage, a more frequent axillary node presentation, higher histologic grade, and higher incidence of triple-negative subtype tumors than older patients and also received more chemotherapy and were less likely to undergo hormone therapy. The younger patients with hormone receptor (HR)-positive tumors showed significantly poorer disease-free survival (DFS), loco-regional recurrence-free survival, distant metastasis-free survival, and breast cancer-specific survival outcomes than older patients. Younger patients with HR-positive and human epidermal growth factor receptor 2 (HER2)-negative tumor subtypes had a significantly improved DFS over time (p = 0.032). Within the HR-positive/Her2-negative subtype, more women received gonadotropin-releasing hormone agonist and tamoxifen treatment from 2003 to 2008 compared with 1989 to 2002 (p = 0.001 and p = 0.075, respectively).

Conclusions

HR-positive young breast cancer patients have a poorer survival compared with older patients, even with more frequent chemotherapy, but more recent use of tamoxifen and ovarian suppression might improve this outcome in these patients.

Keywords

Breast cancer Gonadotropin-releasing hormone Endocrine therapy Young age 

Notes

Compliance with ethical standards

Conflicts of interest

There are no conflicts of interests for all authors.

Supplementary material

10549_2017_4331_MOESM1_ESM.docx (16 kb)
Supplementary material 1 (DOCX 17 kb)

References

  1. 1.
    Fredholm H, Eaker S, Frisell J, Holmberg L, Fredriksson I, Lindman H (2009) Breast cancer in young women: poor survival despite intensive treatment. PLoS ONE 4:e7695. doi: 10.1371/journal.pone.0007695 CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Chen HL, Zhou MQ, Tian W, Meng KX, He HF (2016) Effect of age on breast cancer patient prognoses: a population-based study using the SEER 18 database. PLoS ONE 11:e0165409. doi: 10.1371/journal.pone.0165409 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Sivasubramaniam PG, Zhang BL, Zhang Q, Smith JS, Zhang B, Tang ZH, Chen GJ, Xie XM, Xu XZ, Yang HJ, He JJ, Li H, Li JY, Fan JH, Qiao YL (2015) Breast cancer disparities: a multicenter comparison of tumor diagnosis, characteristics, and surgical treatment in China and the U.S. Oncologist 20:1044–1050. doi: 10.1634/theoncologist.2014-0290 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lee HB, Han W (2014) Unique features of young age breast cancer and its management. J Breast Cancer 17:301–307. doi: 10.4048/jbc.2014.17.4.301 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Sheridan W, Scott T, Caroline S, Yvonne Z, Vanessa B, David V, Karen G, Stephen C (2014) Breast cancer in young women: have the prognostic implications of breast cancer subtypes changed over time? Breast Cancer Res Treat 147:617–629. doi: 10.1007/s10549-014-3125-1 CrossRefPubMedGoogle Scholar
  6. 6.
    Kataoka A, Iwamoto T, Tokunaga E, Tomotaki A, Kumamaru H, Miyata H, Niikura N, Kawai M, Anan K, Hayashi N, Masuda S, Tsugawa K, Aogi K, Ishida T, Masuoka H, Iijima K, Kinoshita T, Nakamura S, Tokuda Y (2016) Young adult breast cancer patients have a poor prognosis independent of prognostic clinicopathological factors: a study from the Japanese Breast Cancer Registry. Breast Cancer Res Treat 160:163–172. doi: 10.1007/s10549-016-3984-8 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evans C, Deacon J, Stratton MR (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 91:943–949CrossRefPubMedGoogle Scholar
  8. 8.
    Malone KE, Daling JR, Neal C, Suter NM, O’Brien C, Cushing-Haugen K, Jonasdottir TJ, Thompson JD, Ostrander EA (2000) Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer 88:1393–1402CrossRefPubMedGoogle Scholar
  9. 9.
    Anders CK, Hsu DS, Broadwater G, Acharya CR, Foekens JA, Zhang Y, Wang Y, Marcom PK, Marks JR, Febbo PG, Nevins JR, Potti A, Blackwell KL (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 CrossRefPubMedGoogle Scholar
  10. 10.
    Collins LC, Marotti JD, Gelber S, Cole K, Ruddy K, Kereakoglow S, Brachtel EF, Schapira L, Come SE, Winer EP, Partridge AH (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 CrossRefPubMedGoogle Scholar
  11. 11.
    Azim HA Jr, Partridge AH (2014) Biology of breast cancer in young women. Breast Cancer Res 16:427. doi: 10.1186/s13058-014-0427-5 CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Aalders KC, Postma EL, Strobbe LJ, van der Heiden-van der Loo M, Sonke GS, Boersma LJ, van Diest PJ, Siesling S, van Dalen T (2016) Contemporary locoregional recurrence rates in young patients with early-stage breast cancer. J Clin Oncol 34:2107–2114. doi: 10.1200/JCO.2015.64.3536 CrossRefPubMedGoogle Scholar
  13. 13.
    Aebi S, Gelber S, Castiglione-Gertsch M, Gelber RD, Collins J, Thurlimann B, Rudenstam CM, Lindtner J, Crivellari D, Cortes-Funes H, Simoncini E, Werner ID, Coates AS, Goldhirsch A (2000) Is chemotherapy alone adequate for young women with oestrogen-receptor-positive breast cancer? Lancet 355:1869–1874. doi: 10.1016/s0140-6736(00)02292-3 CrossRefPubMedGoogle Scholar
  14. 14.
    Ahn SH, Son BH, Kim SW, Kim SI, Jeong J, Ko SS, Han W (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 CrossRefPubMedGoogle Scholar
  15. 15.
    Arvold ND, Taghian AG, Niemierko A, Abi Raad RF, Sreedhara M, Nguyen PL, Bellon JR, Wong JS, Smith BL, Harris JR (2011) Age, breast cancer subtype approximation, and local recurrence after breast-conserving therapy. J Clin Oncol 29:3885–3891. doi: 10.1200/JCO.2011.36.1105 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Partridge AH, Gelber S, Piccart-Gebhart MJ, Focant F, Scullion M, Holmes E, Winer EP, Gelber RD (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 CrossRefPubMedGoogle Scholar
  17. 17.
    Partridge AH, Hughes ME, Warner ET, Ottesen RA, Wong YN, Edge SB, Theriault RL, Blayney DW, Niland JC, Winer EP, Weeks JC, Tamimi RM (2016) Subtype-dependent relationship between young age at diagnosis and breast cancer survival. J Clin Oncol 34:3308–3314. doi: 10.1200/JCO.2015.65.8013 CrossRefPubMedGoogle Scholar
  18. 18.
    Goldhirsch A, Gelber RD, Yothers G, Gray RJ, Green S, Bryant J, Gelber S, Castiglione-Gertsch M, Coates AS (2001) Adjuvant therapy for very young women with breast cancer: need for tailored treatments. J Natl Cancer Inst Monogr 30:44–51CrossRefGoogle Scholar
  19. 19.
    Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, Bonnefoi HR, Climent MA, Da Prada GA, Burstein HJ, Martino S, Davidson NE, Geyer CE Jr, Walley BA, Coleman R, Kerbrat P, Buchholz S, Ingle JN, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Colleoni M, Viale G, Coates AS, Goldhirsch A, Gelber RD (2015) Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med 372:436–446. doi: 10.1056/NEJMoa1412379 CrossRefPubMedGoogle Scholar
  20. 20.
    Regan MM, Francis PA, Pagani O, Fleming GF, Walley BA, Viale G, Colleoni M, Lang I, Gomez HL, Tondini C, Pinotti G, Price KN, Coates AS, Goldhirsch A, Gelber RD (2016) Absolute benefit of adjuvant endocrine therapies for premenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer: TEXT and SOFT trials. J Clin Oncol 34:2221–2231. doi: 10.1200/JCO.2015.64.3171 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Cancello G, Maisonneuve P, Rotmensz N, Viale G, Mastropasqua MG, Pruneri G, Veronesi P, Torrisi R, Montagna E, Luini A, Intra M, Gentilini O, Ghisini R, Goldhirsch A, Colleoni M (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 CrossRefPubMedGoogle Scholar
  22. 22.
    Siu AL, U. S. Preventive Services Task Force (2016) Screening for breast cancer: U.S. preventive services task force recommendation statement. Ann Intern Med 164:279–296. doi: 10.7326/M15-2886 CrossRefGoogle Scholar
  23. 23.
    Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR (2008) 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 26:2373–2378. doi: 10.1200/JCO.2007.14.4287 CrossRefPubMedGoogle Scholar
  24. 24.
    Brollo J, Kneubil MC, Botteri E, Rotmensz N, Duso BA, Fumagalli L, Locatelli MA, Criscitiello C, Lohsiriwat V, Goldhirsch A, Leonardi MC, Orecchia R, Curigliano G (2013) Locoregional recurrence in patients with HER2 positive breast cancer. Breast 22:856–862. doi: 10.1016/j.breast.2013.03.010 CrossRefPubMedGoogle Scholar
  25. 25.
    Kim HJ, Han W, Yi OV, Shin HC, Ahn SK, Koh BS, Moon HG, You JH, Son BH, Ahn SH, Noh DY (2011) 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 130:499–505. doi: 10.1007/s10549-011-1736-3 CrossRefPubMedGoogle Scholar
  26. 26.
    van der Hage JA, Mieog JS, van de Vijver MJ, van de Velde CJ, European Organization for Research Treatment of Cancer (2007) Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis. Breast Cancer Res 9:R70. doi: 10.1186/bcr1778 CrossRefGoogle Scholar
  27. 27.
    Kroman N, Jensen MB, Wohlfahrt J, Mouridsen HT, Andersen PK, Melbye M (2000) Factors influencing the effect of age on prognosis in breast cancer: population based study. BMJ 320:474–478CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kim SW, Chun M, Han S, Jung YS, Choi JH, Kang SY, Yim H, Kang SH (2017) Young age is associated with increased locoregional recurrence in node-positive breast cancer with luminal subtypes. Cancer Res Treat 49:484–493. doi: 10.4143/crt.2016.246 CrossRefPubMedGoogle Scholar
  29. 29.
    Swain SM, Jeong JH, Geyer CE Jr, Costantino JP, Pajon ER, Fehrenbacher L, Atkins JN, Polikoff J, Vogel VG, Erban JK, Rastogi P, Livingston RB, Perez EA, Mamounas EP, Land SR, Ganz PA, Wolmark N (2010) Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 362:2053–2065. doi: 10.1056/NEJMoa0909638 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Pagani O, Regan MM, Walley BA, Fleming GF, Colleoni M, Lang I, Gomez HL, Tondini C, Burstein HJ, Perez EA, Ciruelos E, Stearns V, Bonnefoi HR, Martino S, Geyer CE Jr, Pinotti G, Puglisi F, Crivellari D, Ruhstaller T, Winer EP, Rabaglio-Poretti M, Maibach R, Ruepp B, Giobbie-Hurder A, Price KN, Bernhard J, Luo W, Ribi K, Viale G, Coates AS, Gelber RD, Goldhirsch A, Francis PA (2014) Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 371:107–118. doi: 10.1056/NEJMoa1404037 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Regan MM, Pagani O, Fleming GF, Walley BA, Price KN, Rabaglio M, Maibach R, Ruepp B, Coates AS, Goldhirsch A, Colleoni M, Gelber RD, Francis PA (2013) Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials. Breast 22:1094–1100. doi: 10.1016/j.breast.2013.08.009 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Tae In Yoon
    • 2
  • Ui-Kang Hwang
    • 3
  • Eui Tae Kim
    • 1
  • SaeByul Lee
    • 1
  • Guiyun Sohn
    • 1
  • Beom Seok Ko
    • 1
  • Jong Won Lee
    • 1
  • Byung Ho Son
    • 1
  • Seonok Kim
    • 4
  • Sei Hyun Ahn
    • 1
  • Hee Jeong Kim
    • 1
  1. 1.Division of Breast and Endocrine Surgery, Department of SurgeryUniversity of Ulsan College of MedicineSeoulRepublic of Korea
  2. 2.Department of Surgery, College of MedicineHanyang UniversitySeoulRepublic of Korea
  3. 3.Department of Trauma SurgeryAndong Medical Group HospitalAndongRepublic of Korea
  4. 4.Department of Clinical Epidemiology and Biostatics, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

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