BackgroundTreatment with tamoxifen or chemotherapy reduces the risk of contralateral breast cancer (CBC). However, it is uncertain how long the protection lasts and whether the protective effect is modified by patient, tumor, or treatment characteristics.MethodsThe population-based WECARE Study included 1521 cases with CBC and 2212 age- and year of first diagnosis-matched controls with unilateral breast cancer recruited during two phases in the USA, Canada, and Denmark. Women were diagnosed with a first breast cancer before age 55 years during 1985–2008. Abstraction of medical records provided detailed treatment information, while information on risk factors was obtained during telephone interviews. Risk ratios (RRs) and 95 % confidence intervals (CIs) for CBC were obtained from multivariable conditional logistic regression models.ResultsCompared with never users of tamoxifen, the RR of CBC was lower for current users of tamoxifen (RR = 0.73; 95 % CI = 0.55–0.97) and for past users within 3 years of last use (RR = 0.73; 95 % CI = 0.53–1.00). There was no evidence of an increased risk of estrogen receptor-negative CBC associated with ever use of tamoxifen or use for 4.5 or more years. Use of chemotherapy (ever versus never use) was associated with a significantly reduced RR of developing CBC 1–4 years (RR = 0.59; 95 % CI = 0.45–0.77) and 5–9 years (RR = 0.73; 95 % CI = 0.56–0.95) after first breast cancer diagnosis. RRs of CBC associated with tamoxifen or with chemotherapy use were independent of age, family history of breast cancer, body mass index and tumor characteristics of the first breast cancer with the exception that the RR of CBC was lower for lobular histology compared with other histologies.ConclusionOur findings are consistent with previous studies showing that treatment with tamoxifen or chemotherapy is associated with a lower risk of CBC although the risk reduction appears to last for a limited time period after treatment is completed.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-016-0726-0) contains supplementary material, which is available to authorized users.

Occurrence of cancer in the contralateral breast seems to be rather independent of time passed since the first primary. The finding of a decreasing incidence of CBC after 1997 is likely to be due to more women receiving systemic adjuvant therapy such as tamoxifen and longer duration of this treatment as well as the introduction of aromatase inhibitors.

Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a large population-based case-control study of women with breast cancer where cases (N=1521) had asynchronous CBC and controls (N=2212), matched on survival time and other factors, had unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease characteristics, and other factors. There was some evidence for an association between CBC risk and current drinking or current smoking at the time of first breast cancer diagnosis, but the increased risk occurred primarily among women exposed to both (RR=1.62, 95% CI 1.24–2.11). CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR=1.54, 95% CI 1.18–1.99). In the subset of women with detailed information on amount consumed, smoking an average of ≥10 cigarettes per day following diagnosis was also associated with increased CBC risk (RR=1.50, 95% CI 1.08–2.08; p-trend=0.03). Among women with a diagnosis of breast cancer, information on current drinking and smoking could contribute to the prediction of CBC risk. Women who both drink and smoke may represent a group who merit targeted lifestyle intervention to modify their risk of CBC.

BackgroundStatins have demonstrated antineoplastic effects in breast cancer cell lines, particularly in oestrogen receptor (ER)-negative cell lines. However, epidemiological studies have not supported a preventive effect of statin use against breast cancer. Therefore, we examined the association between statin use and contralateral breast cancer (CBC) risk among women with breast cancer.MethodsWe identified 52,723 women with non-metastatic breast cancer during 1996–2012 from the Danish Breast Cancer Group database. We defined time-varying post-diagnosis statin use as minimum two prescriptions lagged by 1 year. Cox regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with statin use.ResultsStatin use was associated with a lower CBC risk (HR = 0.88; 95% CI = 0.73–1.05). The inverse association was strongest for long-term use overall (HR = 0.64; 95% CI = 0.43–0.96), although the HR specifically for long-term consistent use and high-intensity use approached unity. Among ER-negative breast cancer patients, statin use was associated with a CBC risk reduction (HR = 0.67; 95% CI = 0.45–1.00).ConclusionsWe found some indication that statins reduce the risk of CBC. Further evaluations are needed to disentangle the equivocal results for long-term use and to establish if ER-negative breast cancer patients may benefit most from statin use.

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Breast cancer-specific mortality rates were markedly higher after compared with before a CBC diagnosis. We found higher breast cancer-specific mortality after CBC associated with a short interval between diagnoses among patients diagnosed with CBC before age 70 years.

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Determining how cancer treatments affect the risk of cardiovascular morbidities is essential, and the development of high-quality methods for collecting such data is critical. While self-reported data are adequate for assessing the presence of any CVD condition, medical record review will yield higher quality data on specific CVD conditions.