Willingness of women with early estrogen receptor-positive breast cancer to take adjuvant CDK4/6 inhibitors.

Background: The steady decline in breast cancer (bca) mortality has come at the cost of increasingly toxic and expensive adjuvant therapies. Trials evaluating the addition of 2 or 3 years of cyclin-dependent kinase 4/6 (cdk4/6) inhibitors to adjuvant endocrine therapy (et) are ongoing, but the willingness of patients to take such additional therapy is unknown. Methods: We surveyed 100 consecutive postmenopausal women with nonmetastatic estrogen receptor-positive bca who had initiated adjuvant et within the preceding 2 years. Participants were asked about perceived recurrence risk, bca worry, and overall health. They were then asked about their willingness to accept 2 years of treatment with an additional oral drug that would reduce recurrence by 40% for a range of baseline recurrence risks in 2 hypothetical scenarios. Results: Mean age of the 99 evaluable participants was 61.7 years. In the scenario with no drug toxicity, 85% of respondents were likely to accept the new drug for a reduction in recurrence to 30% from 50%, but only 49% would take the drug if risk was reduced to 3% from 5%. In a scenario with drug-induced fatigue, the corresponding drug acceptance rates were 55% and 39% respectively. For the second scenario, bca worry was correlated with increased willingness to take the drug, even for only a 2% absolute reduction in recurrence risk. Conclusions: The willingness of patients with estrogen receptor-positive bca to take an adjuvant cdk4/6 inhibitor will greatly depend on the expected benefit and toxicities described to them as well as on worry about bca recurrence.

A population-based analysis of breast cancer incidence and survival by subtype in Ontario women.

Background: Breast cancer (bca) is the type of cancer most frequently diagnosed among women in Canada. Breast cancer is categorized into various molecular subtypes by the expression of estrogen receptor (er), progesterone receptor (pgr), and her2 (human epidermal growth factor receptor 2). Currently, Canada has no national cancer registry with epidemiology data by subtype. Thus, we conducted a study to determine incidence, survival, and clinicopathologic characteristics by bca subtype [triple negative breast cancer (tnbc); her2+; and hormone receptor-positive (hr+), her2-] in Canadian women newly diagnosed with bca. Methods: Female patients diagnosed between 1 April 2012 and 31 March 2016 (fiscal 2012-2015) were identified in the Ontario Cancer Registry, and individual patient data were linked to data in provincial health administrative databases. Descriptive statistics and Kaplan-Meier curves were generated. Results: In this cohort, 3277 women (9.5%) had tnbc, 4902 (14.3%) had her2+ bca, and 22,247 (64.8%) had hr+, her2-breast cancer. The annual incidence was 15 per 100,000 for the tnbc group, 21-23 per 100,000 for the her2+ group, and 97-105 per 100,000 for the hr+, her2- group. The lowest median overall survival (mos) of 8.9 months was observed in women with clinical stage iv tnbc. In comparison, the mos was 37.3 months in those with her2+ disease and 35.2 months in those with and hr+, her2- metastatic bca. Conclusions: In the present study, the most recent and largest administrative database analysis of a Canadian population to date, we observed a subtype distribution consistent with previously reported data, together with comparable annual incidence and overall survival patterns.

Cognitive effects of adjuvant endocrine therapy in older women treated for early-stage breast cancer: a 1-year longitudinal study.

PURPOSE: Evidence suggests endocrine therapy (ET) for breast cancer (BC) has adverse cognitive effects, but its specific effects on older women are unknown. This is despite the fact that older women are at increased risk of both breast cancer (BC) and cognitive decline relative to younger women. This study prospectively examined the cognitive effects of ET in a cohort of older BC patients. Our primary outcome measure was change in verbal memory, the cognitive domain most consistently affected by estrogen deprivation. METHODS: Forty-two chemotherapy-naïve women age 60+, without dementia and recently diagnosed with hormone receptor-positive BC, completed neuropsychological tests at the time of ET initiation and after 1 year of treatment. Change in age-standardized verbal memory performance was examined using paired t tests. To assess a broader range of potential cognitive effects, we also examined changes in visual memory, processing speed, frontal executive function, and perceptual reasoning. RESULTS: Participants exhibited significant decline from baseline to 1 year in verbal memory (p = 0.01). This decline was small to moderate in effect size (d = - 0.40). Performance on other domains did not change significantly over the year (all p > 0.05). CONCLUSIONS: Our findings suggest potentially detrimental effects of ET on verbal memory in older women after just 1 year of treatment. Given that ET is prescribed for courses of 5 to 10 years, additional studies examining longer-term effects of treatment in older women are critical.

Thyroid hormone receptor beta-1 expression in early breast cancer: a validation study.

PURPOSE: Preliminary data suggest that high expression of the TRß1 tumor suppressor is associated with longer survival among women with early breast cancer. We undertook this study to validate these findings. METHODS: In this prospective cohort study, we analyzed the prognostic significance of TRß1 protein expression in the breast tumors of 796 women who had undergone breast surgery in the Henrietta Banting Breast Cancer database. All women were recruited after undergoing primary surgical therapy at Women's College Hospital (Toronto, ON, Canada) between January 1987 and December 2000. Details regarding patient age at diagnosis, systemic, and local therapies, as well as pathological features of their tumor have been systematically recorded. Clinical outcomes including breast cancer recurrence and death have been updated at least once each year with a median follow-up of 9.6 years (range 0.1-21 years). RESULTS: High TRß1 expression (> 4 on the Allred score) was associated with a longer breast cancer-specific survival with a HR 0.45 (95% CI 0.33-0.61), p < 0.0001 in a univariable Cox regression model. This was maintained in a multivariable model adjusted for age, tumor size, nodal status, chemotherapy, hormone therapy, radiotherapy, surgery, and ER status with a HR of 0.61 (95% CI 0.44-0.85), p = 0.004. CONCLUSIONS: High expression of TRß1 is associated with longer breast cancer-specific survival independent of other prognostic factors. Given that low TRß expression is associated with chemotherapy resistance in-vitro, TRß1 may also serve as a predictive biomarker or even a therapeutic target given the availability of TRß agonists.

Ataxia-telangiectasia gene (ATM) mutation heterozygosity in breast cancer: a narrative review.

Background: Despite the fact that heterozygosity for a pathogenic ATM variant is present in 1%-2% of the adult population, clinical guidelines to inform physicians and genetic counsellors about optimal management in that population are lacking. Methods: In this narrative review, we describe the challenges and controversies in the management of women who are heterozygous for a pathogenic ATM variant with respect to screening for breast and other malignancies, to choices for systemic therapy, and to decisions about radiation therapy. Results: Given that the lifetime risk for breast cancer in women who are heterozygous for a pathogenic ATM variant is likely greater than 25%, those women should undergo annual mammographic screening starting at least by 40 years of age. For women in this group who have a strong family history of breast cancer, earlier screening with both magnetic resonance imaging and mammography should be considered. High-quality data to inform the management of established breast cancer in carriers of pathogenic ATM variants are lacking. Although deficiency in the ATM gene product might confer sensitivity to dna-damaging pharmaceuticals such as inhibitors of poly (adp-ribose) polymerase or platinum agents, prospective clinical trials have not been conducted in the relevant patient population. Furthermore, the evidence with respect to radiation therapy is mixed; some data suggest increased toxicity, and other data suggest improved clinical benefit from radiation in women who are carriers of a pathogenic ATM variant. Conclusions: As in the 2017 U.S. National Comprehensive Cancer Network guidelines, we recommend high-risk imaging for women in Ontario who are heterozygous for a pathogenic ATM variant. Currently, ATM carrier status should not influence decisions about systemic or radiation therapy in the setting of an established breast cancer diagnosis.