Despite the benefit of adjuvant hormonal therapy (HT) on mortality among women with breast cancer (BC), many women are non-adherent with its use. We investigated the effects of early discontinuation and non-adherence to HT on mortality in women enrolled in Kaiser Permanente of Northern California (KPNC). We identified women diagnosed with hormone-sensitive stage I–III BC, 1996–2007, and used automated pharmacy records to identify prescriptions and dates of refill. We categorized patients as having discontinued HT early if 180 days elapsed from the prior prescription. For those who continued, we categorized patients as adherent if the medication possession ratio was ≥80%. We used Cox proportional hazards models to estimate the association between discontinuation and non-adherence with all-cause mortality. Among 8,769 women who filled at least one prescription for HT, 2,761 (31%) discontinued therapy. Of those who continued HT, 1,684 (28%) were non-adherent. During a median follow-up of 4.4 years, 813 women died. Estimated survival at 10 years was 80.7% for women who continued HT versus 73.6% for those who discontinued (P < 0.001). Of those who continued, survival at 10 years was 81.7 and 77.8% in women who adhered and non-adhered, respectively (P < 0.001). Adjusting for clinical and demographic variables, both early discontinuation (HR 1.26, 95% CI 1.09–1.46) and non-adherence (HR 1.49, 95% CI 1.23–1.81), among those who continued, were independent predictors of mortality. Both early discontinuation and non-adherence to HT were common and associated with increased mortality. Interventions to improve continuation of and adherence to HT may be critical to improve BC survival.

A B S T R A C T PurposeWhile studies have found that adjuvant hormonal therapy for hormone-sensitive breast cancer (BC) dramatically reduces recurrence and mortality, adherence to medications is suboptimal. We investigated the rates and predictors of early discontinuation and nonadherence to hormonal therapy in patients enrolled in Kaiser Permanente of Northern California health system. Patients and MethodsWe identified women diagnosed with hormone-sensitive stage I-III BC from 1996 to 2007 and used automated pharmacy records to identify hormonal therapy prescriptions and dates of refill. We used Cox proportional hazards regression models to analyze factors associated with early discontinuation and nonadherence (medication possession ratio Ͻ 80%) of hormonal therapy. ResultsWe identified 8,769 patients with BC who met our eligibility criteria and who filled at least one prescription for tamoxifen (43%), aromatase inhibitors (26%), or both (30%) within 1 year of diagnosis. Younger or older age, lumpectomy (v mastectomy), and comorbidities were associated with earlier discontinuation, while Asian race, being married, earlier year at diagnosis, receipt of chemotherapy or radiotherapy, and longer prescription refill interval were associated with completion of 4.5 years of therapy. Of those who continued therapy, similar factors were associated with full adherence. Women age younger than 40 years had the highest risk of discontinuation (hazard ratio, 1.51; 95% CI, 1.23 to 1.85). By 4.5 years, 32% discontinued therapy, and of those who continued, 72% were fully adherent. ConclusionOnly 49% of patients with BC took adjuvant hormonal therapy for the full duration at the optimal schedule. Younger women are at high risk of nonadherence. Interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women.

Testosterone is important for the development of secondary sexual characteristics in female-to-male (FtM) transsexuals, but it may increase breast cancer risk. To date, only one breast cancer case has been reported in the literature in a FtM transsexual after 10 years of testosterone therapy. We describe 2 cases of breast cancers diagnosed in FtM transsexuals who have been treated with supraphysiological doses of testosterone. Our 2 cases demonstrate the unique issues that concern the management of FtM transsexuals with breast cancer and examine possible roles of testosterone in the development of breast cancer.

ABSTRACT

OBJECTIVES:Cholecystectomy has been implicated as a possible risk factor for colorectal cancer. However, the clinical evidence and the underlying mechanism for this association are still inconclusive. We conducted a population-based study to further clarify this association. METHODS:We conducted a retrospective cohort study among all patients aged 40 yr or older in the General Practice Research Database from the United Kingdom. We excluded patients with <1 yr of colorectal cancer-free database follow-up as well as those patients who developed colorectal cancer within 1 yr after their cholecystectomies. Crude and adjusted incidence rate ratios (IRRs) were determined using Poisson regression. RESULTS:The incidence rate of colorectal cancer among cholecystectomy patients (n = 55,960) was 119 (95% CI: 106-133) per 100,000 person-years, compared to 86 (95% CI: 83-90) per 100,000 person-years among patients without a cholecystectomy (n = 574,668). Among the covariates examined, only sex and age were significant confounders and were included in the adjusted analyses. The adjusted IRR of colorectal cancer associated with cholecystectomy was 1.32 (95% CI: 1.16-1.48, p < 0.001). The positive association was present for colon cancer (adjusted IRR 1.51, 95% CI: 1.30-1.74, p < 0.001), but not for rectal cancer (adjusted IRR 1.00, 95% CI: 0.85-1.17, p = 0.99). The pattern of association was similar in men versus women. A similar association with colon cancer was observed for cholelithiasis.CONCLUSIONS: Cholecystectomy is associated with a modestly increased risk of colon cancer but not for rectal cancer. Lithogenic bile could be the underlying mechanism.(Am J Gastroenterol 2005;100:1813-1820)