Background: Organophosphate pesticides (OPs) are one of the most commonly used classes of insecticides in the U.S., and metabolites of OPs have been detected in the urine of >75% of the U.S. population. While studies have shown that OP exposure is associated with risk of neurological diseases and some cancers, the relationship between OP exposure and breast cancer risk is not well understood. Methods: The aim of this rapid review was to systematically evaluate published literature on the relationship between OP exposure and breast cancer risk, including both epidemiologic and laboratory studies. Twenty-seven full-text articles were reviewed by searching on Pubmed, EMBASE, and Cochrane databases. Results: Some human studies showed that malathion, terbufos, and chlorpyrifos were positively associated with human breast cancer risk, and some laboratory studies demonstrated that malathion and chlorpyrifos have estrogenic potential and other cancer-promoting properties. However, the human studies were limited in number, mostly included agricultural settings in several geographical areas in the U.S., and did not address cumulative exposure. Conclusions: Given the mixed results found in both human and laboratory studies, more research is needed to further examine the relationship between OP exposure and breast cancer risk, especially in humans in non-agricultural settings.

Evidence has accumulated showing that recreational physical activity reduces breast cancer risk. However, it is unclear whether risk reduction pertains to specific receptor-defined subtypes. Moreover, few studies have examined whether changes in the amount of recreational physical activity during adulthood influence breast cancer risk. A total of 108,907 women, ages 22 to 79 years with no history of breast cancer when joining the California Teachers Study in 1995–1996, completed a baseline questionnaire and were eligible for the study. Through 2012, 5882 women were diagnosed with invasive breast cancer. Breast cancer subtypes were defined by the expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Multivariable Cox proportional hazards models provided adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) for breast cancer overall and ER/PR/HER2-defined subtypes associated with long-term (from high school through age 54 or age at cohort entry, whichever was younger) and baseline (during 3 years prior to baseline) recreational physical activity. Among women who also completed a follow-up questionnaire at 10 years after baseline in 2005–2008 (54,686 women, 1406 with invasive breast cancer), risk associated with changes in the amount of recreational physical activity from baseline to the 10-year follow-up (during 3 years prior to the 10-year follow-up) was determined. Both long-term and baseline strenuous recreational physical activity were inversely associated with risk of invasive breast cancer (P trend ≤0.03). The observed associations were mainly confined to women with triple negative breast cancer (TNBC, ER–/PR–/HER2–, P trend ≤0.02) or luminal A-like subtype (ER+ or PR+ plus HER2–) who were former users of menopausal hormone therapy at baseline (P trend = 0.02, P homogeneity of trends ≤0.03). Moreover, women who consistently engaged in the highest level (≥3.51 h/wk/y) of strenuous recreational physical activity between baseline and 10-year follow-up had the lowest risk of breast cancer (HR = 0.71, 95 % CI = 0.52–0.98) when compared to those who were consistently low (≤0.50 h/wk/y). Strenuous recreational physical activity is associated with lower breast cancer risk, especially TNBC. The benefit may be maximized by consistently engaging in high-intensity recreational physical activity during adulthood.

Environmental and lifestyle factors are believed to account for >80% of breast cancers; however, it is not well understood how and when these factors affect risk and which exposed individuals will actually develop the disease. While alcohol consumption, obesity, and hormone therapy are some known risk factors for breast cancer, other exposures associated with breast cancer risk have not yet been identified or well characterized. In this paper, it is proposed that the identification of blood epigenetic markers for personal, in utero, and ancestral environmental exposures can help researchers better understand known and potential relationships between exposures and breast cancer risk and may enable personalized prevention strategies.

The ability of tamoxifen and raloxifene to decrease breast cancer risk varies among different breast cancer subtypes. It is important to determine one’s subtype-specific breast cancer risk when considering chemoprevention. A number of single nucleotide polymorphisms (SNPs), including one in caspase-8 (CASP8), have been previously associated with risk of developing breast cancer. Because caspase-8 is an important protein involved in receptor-mediated apoptosis whose activity is affected by estrogen, we hypothesized that additional SNPs in CASP8 could be associated with breast cancer risk, perhaps in a subtype-specific manner. Twelve tagging SNPs of CASP8 were analyzed in a nested case control study (1,353 cases and 1,384 controls) of non-Hispanic white women participating in the California Teachers Study. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for each SNP using all, estrogen receptor (ER)-positive, ER-negative, human epidermal growth factor receptor 2 (HER2)-positive, and HER2-negative breast cancers as separate outcomes. Several SNPs were associated with all, ER-positive, and HER2-positive breast cancers; however, after correcting for multiple comparisons (i.e., p < 0.0008), only rs2293554 was statistically significantly associated with HER2-positive breast cancer (OR = 1.98, 95 % CI 1.34-2.92, uncorrected p = 0.0005). While our results for CASP8 SNPs should be validated in other cohorts with subtype-specific information, we conclude that some SNPs in CASP8 are associated with subtype-specific breast cancer risk. This study contributes to our understanding of CASP8 SNPs and breast cancer risk by subtype.

Although it is known that the risk of a second breast cancer event among young women diagnosed with ductal carcinoma in situ (DCIS) is higher than in older women, the effect of current treatment options on long-term outcomes in this subgroup of women remains poorly defined. We aimed to evaluate national treatment trends and determine their effect on second breast cancer risk and overall survival among young women diagnosed with DCIS. Surveillance, Epidemiology, and End Results data from 1998 to 2011 were used to analyze 3648 DCIS patients younger than age 40 years. Among all treatment options, breast-conserving surgery (BCS) with radiation therapy (BCS + RT) was the most prevalent (36.1%) followed by mastectomy (MTX) without contralateral prophylactic MTX (CPM; 25.8%), BCS alone (22.2%), and MTX with CPM (15.8%). Risk of a second ipsilateral event was > 5-fold and > 2-fold lower within 2 years and 5 years of initial DCIS diagnosis, respectively, in women who received BCS + RT compared with BCS alone; and overall survival was 3-fold higher in women who received BCS + RT. However, MTX with or without CPM did not show an increase in overall survival compared with BCS + RT. In addition, although the percentage of young women who receive MTX with CPM has increased in recent years, MTX with CPM did not show an increased benefit in survival compared with MTX without CPM. The results of our study suggest that more aggressive treatments do not offer survival benefits over BCS + RT; thus, clinical treatment options in young women with DCIS should be carefully considered.