Age-related risk factors associated with primary contralateral breast cancer among younger women versus older women
Contralateral prophylactic mastectomy is increasing, despite unclear evidence of improving survival. To investigate the age-related risk factors for contralateral breast cancer (CBC).
This study included 8716 patients diagnosed with non-metastatic unilateral invasive breast cancer between 1989 and 2008. Data on primary tumor size, node metastasis, grade and subtype using individual matching were used to adjust for differences in the primary tumor and treatment between younger and older age groups. CBC risk factors, CBC-free survival, and annual CBC risk were analyzed by age.
The younger group included 652 patients aged under 35 years, and the older group included 2608 women aged 35 years or older. The median time to CBC development was 6.1 years. CBC was detected in 6.6% of the women in the younger group and 2.5% of those in the older group. Multivariable analysis revealed a relative CBC risk of 2.48 in younger women compared to older women. The risk was significantly higher among women with human epidermal growth factor receptor 2 (HER2)-overexpressing tumors (hazard ratio [HR] 4.98), a family history of breast cancer (HR 7.79), and anti-hormone therapy (HR 3.46). In younger women with HER2-positive cancer, CBC occurrence peaked at 4.6 years after surgery, in those with hormone receptor-positive cancer, it peaked at 7.1 years after surgery, and in triple-negative disease cases, and it increased steadily over time.
After adjusting for primary breast tumor characteristics, patients < 35 years old had 2.5 times the risk of CBC development compared to the older women. CBC occurrence peaked within 5 years after primary breast cancer in younger women with the HER2-positive subtype and after 5 years in cases with the hormone receptor-positive subtype.
KeywordsYoung breast cancer Contralateral breast cancer HER2/neu Metachronous
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Compliance with ethical standards
Conflict of interest
The authors declare that they have conflict of interest
Research involving human participants and/or animals
This article does not contain any studies with human participants performed by any of the authors.
- 1.Bernstein JL, Lapinski RH, Thakore SS, Doucette JT, Thompson WD (2003) The descriptive epidemiology of second primary breast cancer. Epidemiology 14:552–558. https://doi.org/10.1097/01.ede.0000072105.39021.6d CrossRefPubMedGoogle Scholar
- 3.Bessonova L, Taylor TH, Mehta RS, Zell JA, Anton-Culver H (2011) Risk of a second breast cancer associated with hormone-receptor and HER2/neu status of the first breast cancer. Cancer Epidemiol Biomarkers Prev 20:389–396. https://doi.org/10.1158/1055-9965.epi-10-1016 CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Gierach GL, Curtis RE, Pfeiffer RM et al (2017) Association of adjuvant tamoxifen and aromatase inhibitor therapy with contralateral breast cancer risk among US women with breast cancer in a general community setting. JAMA Oncol 3:186–193. https://doi.org/10.1001/jamaoncol.2016.3340 CrossRefPubMedGoogle Scholar
- 6.Saltzman BS, Malone KE, McDougall JA, Daling JR, Li CI (2012) Estrogen receptor, progesterone receptor, and HER2-neu expression in first primary breast cancers and risk of second primary contralateral breast cancer. Breast Cancer Res Treat 135:849–855. https://doi.org/10.1007/s10549-012-2183-5 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Rusner C, Wolf K, Bandemer-Greulich U, Engel J, Stegmaier C, Holleczek B, Schubert-Fritschle G, Tillack A, Stang A (2014) Risk of contralateral second primary breast cancer according to hormone receptor status in Germany. Breast Cancer Res 16:452. https://doi.org/10.1186/s13058-014-0452-4 CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Giuliano AE, Boolbol S, Degnim A, Kuerer H, Leitch AM, Morrow M (2007) Society of Surgical Oncology: position statement on prophylactic mastectomy. approved by the Society of Surgical Oncology Executive Council, March 2007. Ann Surg Oncol 14:2425–2427. https://doi.org/10.1245/s10434-007-9447-z CrossRefPubMedGoogle Scholar
- 19.Morrow M (2011) Prophylactic mastectomy of the contralateral breast. Breast 20 Suppl 3:S108–S110. https://doi.org/10.1016/s0960-9776(11)70306-x
- 20.Kurian AW, Lichtensztajn DY, Keegan TH, Nelson DO, Clarke CA, Gomez SL (2014) Use of and mortality after bilateral mastectomy compared with other surgical treatments for breast cancer in California, 1998–2011. Jama 312:902–914. https://doi.org/10.1001/jama.2014.10707 CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Kim HJ, Han W, Yi OV et al (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. https://doi.org/10.1007/s10549-011-1736-3 CrossRefPubMedGoogle Scholar
- 22.Kheirelseid EA, Jumustafa H, Miller N, Curran C, Sweeney K, Malone C, McLaughlin R, Newell J, Kerin MJ (2011) Bilateral breast cancer: analysis of incidence, outcome, survival and disease characteristics. Breast Cancer Res Treat 126:131–140. https://doi.org/10.1007/s10549-010-1057-y CrossRefPubMedGoogle Scholar
- 23.Killelea BK, Chagpar AB, Horowitz NR, Lannin DR (2017) Characteristics and treatment of human epidermal growth factor receptor 2 positive breast cancer: 43,485 cases from the National Cancer Database treated in 2010 and 2011. Am J Surg 213:426–432. https://doi.org/10.1016/j.amjsurg.2016.05.018 CrossRefPubMedGoogle Scholar
- 27.Rhiem K, Engel C, Graeser M et al (2012) The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study. Breast Cancer Res 14:R156. https://doi.org/10.1186/bcr3369 CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Molina-Montes E, Perez-Nevot B, Pollan M, Sanchez-Cantalejo E, Espin J, Sanchez MJ (2014) Cumulative risk of second primary contralateral breast cancer in BRCA1/BRCA2 mutation carriers with a first breast cancer: a systematic review and meta-analysis. Breast 23:721–742. https://doi.org/10.1016/j.breast.2014.10.005 CrossRefPubMedGoogle Scholar
- 31.Davies C, Pan H, Godwin J et al (2013) 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 381:805–816. https://doi.org/10.1016/s0140-6736(12)61963-1 CrossRefPubMedPubMedCentralGoogle Scholar