Breast Cancer Research and Treatment

, Volume 105, Issue 2, pp 195-207

First online:

Breast cancer risk factors and second primary malignancies among women with breast cancer

  • Amy Trentham-DietzAffiliated withPaul P. Carbone Comprehensive Cancer Center, University of WisconsinDepartment of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin Email author 
  • , Polly A. NewcombAffiliated withPaul P. Carbone Comprehensive Cancer Center, University of WisconsinCancer Prevention Program, Fred Hutchinson Cancer Research Center
  • , Hazel B. NicholsAffiliated withPaul P. Carbone Comprehensive Cancer Center, University of Wisconsin
  • , John M. HamptonAffiliated withPaul P. Carbone Comprehensive Cancer Center, University of Wisconsin

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To examine the association between breast cancer risk factors and second primary cancers (independent diagnoses occurring at least 12 months after the initial breast cancer diagnosis) among breast cancer survivors.


In this population-based study, cancer outcomes among breast cancer survivors first diagnosed during 1987–2000 were investigated. Invasive breast cancer cases were identified from the statewide tumor registry and interviewed regarding their pre-diagnosis risk factors, including reproductive and lifestyle characteristics, approximately 1 year after diagnosis. Data on second primary cancers (not recurrences) and deaths were obtained by linkage with tumor registry reports and death certificates through December 31, 2002. Hazard ratios (HR) were estimated using proportional hazards regression stratified by age and adjusted for stage and other factors.


Among the 10,953 breast cancer cases, 10.8% experienced a second cancer diagnosis within an average of 7 years (including 488 breast, 132 colorectal, 113 endometrial, and 36 ovarian cancers). Risk of a second primary breast cancer increased according to low parity (P = 0.002), older age at menopause (P = 0.08), greater body mass index (P = 0.003) and adult weight gain (P = 0.02), and a family history of breast cancer-particularly among women with 2 or more first-degree affected relatives (HR = 1.8, 95% CI: 1.1–2.9). Reduced risk of colorectal cancer after breast cancer was observed in relation to older ages at menarche (P = 0.05), younger age at menopause (P = 0.04), postmenopausal hormone use (HR = 0.4, 95% CI: 0.3–0.7), normal body mass index (P = 0.07), and infrequent alcohol consumption (P = 0.01). Second endometrial cancer risk was associated with increasing body mass index (P < 0.01) and adult weight gain (P = 0.03). Risk of second ovarian cancer appeared related to recent alcohol intake and family history of breast cancer. Women who reported consuming any alcohol appeared to have a 55% reduction in ovarian cancer risk (95% CI: 0.2–1.0) compared to non-drinkers, while having 2 or more first-degree relatives with breast cancer was associated with an increased risk of ovarian cancer (HR = 4.3, 95% CI: 1.3–14.6).


This study suggests that family history of breast cancer as well as potentially modifiable characteristics including body weight, alcohol intake, and postmenopausal hormone use may be associated with risk of a second cancer diagnosis among breast cancer cases.


Neoplasms Second primary Breast neoplasms Body mass index Body weight Weight gain Body height Alcoholic beverages