Incident comorbidities after tamoxifen or aromatase inhibitor therapy in a racially and ethnically diverse cohort of women with breast cancer.

PURPOSE: As survival with early-stage, hormone receptor (HR)-positive breast has improved, it is essential to understand the long-term risks of incident comorbidities with different adjuvant endocrine therapy (ET) options. METHODS: Women treated with tamoxifen and/or an aromatase inhibitor (AI) for stages 1-3, HR-positive/HER2-negative breast cancer from 2000 to 2016 in either of two healthcare systems in the San Francisco Bay Area were included. We considered the following comorbidities: cerebrovascular accidents, congestive heart failure, dementia, depression/anxiety, diabetes mellitus, hyperlipidemia, myocardial infarction, non-alcoholic steatohepatitis, osteoporosis/fracture, peripheral vascular disease, and venous thromboembolism. Cause-specific Cox proportional hazards models were fit to time-to-new-diagnosis for each comorbidity, accounting for death as a competing risk. Hazard ratios (HR) and 95% confidence intervals (CI) for tamoxifen versus AI were reported. RESULTS: Among 2,902 analyzed patients, the median age at diagnosis was 58.3 years; 67.6% were non-Hispanic white, 22.3% Asian, 7.5% Hispanic, and 1.7% non-Hispanic Black. Half (54.7%) used AIs only, 27.6% used tamoxifen only and 17.7% used both tamoxifen and AIs sequentially. Tamoxifen was associated with a lower risk of osteoporosis than AI (multivariable HR 0.45, 95% CI 0.32-0.62). No other incident comorbidity risk varied between users of tamoxifen versus AIs. CONCLUSION: In a diverse, multi-institutional, contemporary breast cancer cohort, the only incident comorbidity that differed between ET options was osteoporosis, a known side effect of AIs. These results may inform clinical decision-making about ET, and reassure patients who have bothersome symptoms on AIs that they are unlikely to develop worse comorbidities if they switch to tamoxifen.

Simulation modeling of breast cancer endocrine therapy duration by patient and tumor characteristics.

BACKGROUND: Extending endocrine therapy from 5 to 10 years is recommended for women with invasive estrogen receptor (ER)-positive breast cancers. We evaluated the benefits and harms of the five additional years of therapy. METHODS: An established Cancer Intervention and Surveillance Network (CISNET) model used a lifetime horizon with national and clinical trial data on treatment efficacy and adverse events and other-cause mortality among multiple birth cohorts of U.S. women ages 25-79 newly diagnosed with ER+, non-metastatic breast cancer. We assumed 100% use of therapy. Outcomes included life years (LYs), quality-adjusted life years (QALYs), and breast cancer mortality. Results were discounted at 3%. Sensitivity analyses tested a 15-year time horizon and alternative assumptions. RESULTS: Extending tamoxifen therapy duration among women ages 25-49 reduced the lifetime probability of breast cancer death from 11.9% to 9.3% (absolute difference 2.6%). This translates to a gain of 0.77 LYs (281 days)/woman (undiscounted). Adverse events reduce this gain to 0.44 QALYs and after discounting, gains are 0.20 QALYs (73 days)/woman. Extended aromatase inhibitor therapy in women 50-79 had small absolute benefits and gains were offset by adverse events (loss of 0.06 discounted QALYs). There were greater gains with extended endocrine therapy for women with node-positive versus negative cancers, but only women ages 25-49 and 50-59 had a net QALY gain. All gains were reduced with less than 100% treatment completion. CONCLUSION: The extension of endocrine therapy from 5 to 10 years modestly improved lifetime breast cancer outcomes, but in some women, treatment-related adverse events may outweigh benefits.

Receipt of guideline-concordant care among young adult women with breast cancer.

BACKGROUND: Little is known about the real-world care of young adult (YA) females (aged 20-39 years) with breast cancer. This study describes factors associated with the receipt of guideline-concordant care (GCC) among YAs. METHODS: The authors identified 1259 YA women with invasive breast cancer diagnosed in 2013 in the National Cancer Institute's Patterns of Care study. Hospital records were re-abstracted, and treatment was verified. Using the National Comprehensive Cancer Network's 2013 breast cancer guidelines, the authors assessed the receipt of GCC by cancer subtype among a subset of YAs (n = 952). Associations between sociodemographic and clinical factors and GCC receipt were examined. RESULTS: Most YAs were 35 to 39 years old (51.2%) and partnered (56.4%); half had hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) tumors. GCC was found for 81.7% of YAs. Relationships between sociodemographic and clinical factors and GCC receipt differed by subtype. Stage was the only significant predictor of GCC receipt for all subtypes (stage II vs III: odds ratio [OR] for HR+/HER2+, 0.20; 95% confidence interval [CI], 0.08-0.50; OR for HR-/HER2+, 0.13; 95% CI, 0.07-0.25; OR for HR-/HER2-, 3.86; 95% CI, 1.55-9.62; OR for HR+/HER2-, 2.81; 95% CI, 1.63-5.80). CONCLUSIONS: GCC is high among YAs with breast cancer. The effects of sociodemographic factors and treatment facility size on GCC differ by subtype. Consistent with recommendations, tumor biology, not age, is associated with GCC for all subtypes. Future studies should assess the effect of GCC on survival among YAs.

Multicenter Prospective Cohort Study of the Diagnostic Yield and Patient Experience of Multiplex Gene Panel Testing For Hereditary Cancer Risk.

PURPOSE: Multiplex gene panel testing (MGPT) allows for the simultaneous analysis of germline cancer susceptibility genes. This study describes the diagnostic yield and patient experiences of MGPT in diverse populations. PATIENTS AND METHODS: This multicenter, prospective cohort study enrolled participants from three cancer genetics clinics-University of Southern California Norris Comprehensive Cancer Center, Los Angeles County and University of Southern California Medical Center, and Stanford Cancer Institute-who met testing guidelines or had a 2.5% or greater probability of a pathogenic variant (N = 2,000). All patients underwent 25- or 28-gene MGPT and results were compared with differential genetic diagnoses generated by pretest expert clinical assessment. Post-test surveys on distress, uncertainty, and positive experiences were administered at 3 months (69% response rate) and 1 year (57% response rate). RESULTS: Of 2,000 participants, 81% were female, 41% were Hispanic, 26% were Spanish speaking only, and 30% completed high school or less education. A total of 242 participants (12%) carried one or more pathogenic variant (positive), 689 (34%) carried one or more variant of uncertain significance (VUS), and 1,069 (53%) carried no pathogenic variants or VUS (negative). More than one third of pathogenic variants (34%) were not included in the differential diagnosis. After testing, few patients (4%) had prophylactic surgery, most (92%) never regretted testing, and most (80%) wanted to know all results, even those of uncertain significance. Positive patients were twice as likely as negative/VUS patients (83% v 41%; P < .001) to encourage their relatives to be tested. CONCLUSION: In a racially/ethnically and socioeconomically diverse cohort, MGPT increased diagnostic yield. More than one third of identified pathogenic variants were not clinically anticipated. Patient regret and prophylactic surgery use were low, and patients appropriately encouraged relatives to be tested for clinically relevant results.

What Factors Influence Women's Perceptions of their Systemic Recurrence Risk after Breast Cancer Treatment?

BACKGROUND: Breast cancer patients' misunderstanding of their systemic cancer recurrence risk has consequences on decision-making and quality of life. Little is known about how women derive their risk estimates. METHODS: Using Los Angeles and Georgia's SEER registries (2014-2015), a random sample of early-stage breast cancer patients was sent surveys about 2 to 3 months after surgery ( N = 3930; RR, 68%). We conducted an inductive thematic analysis of open-ended responses about why women chose their risk estimates in a uniquely large sub-sample ( N = 1,754). Clinician estimates of systemic recurrence risk were provided for patient sub-groups with DCIS and with low-, intermediate-, and high-risk invasive disease. Women's perceived risk of systemic recurrence (0% to 100%) was categorized as overestimation, reasonably accurate estimation, or underestimation (0% for invasive disease) and was compared across identified factors and by clinical presentation. RESULTS: Women identified 9 main factors related to their clinical experience (e.g., diagnosis and testing; treatment) and non-clinical beliefs (e.g., uncertainty; spirituality). Women who mentioned at least one clinical experience factor were significantly less likely to overestimate their risk (12% v. 43%, P < 0.001). Most women who were influenced by "communication with a clinician" had reasonably accurate recurrence estimates (68%). "Uncertainty" and "family and personal history" were associated with overestimation, particularly for women with DCIS (75%; 84%). "Spirituality, religion, and faith" was associated with an underestimation of risk (63% v. 20%, P < 0.001). LIMITATIONS: The quantification of our qualitative results is subject to any biases that may have occurred during the coding process despite rigorous methodology. CONCLUSIONS: Patient-clinician communication is important for breast cancer patients' understanding of their numeric risk of systemic recurrence. Clinician discussions about recurrence risk should address uncertainty and relevance of family and personal history.

Payer Coverage for Hereditary Cancer Panels: Barriers, Opportunities, and Implications for the Precision Medicine Initiative.

Background: Hereditary cancer panels (HCPs), testing for multiple genes and syndromes, are rapidly transforming cancer risk assessment but are controversial and lack formal insurance coverage. We aimed to identify payers' perspectives on barriers to HCP coverage and opportunities to address them. Comprehensive cancer risk assessment is highly relevant to the Precision Medicine Initiative (PMI), and payers' considerations could inform PMI's efforts. We describe our findings and discuss them in the context of PMI priorities. Methods: We conducted semi-structured interviews with 11 major US payers, covering >160 million lives. We used the framework approach of qualitative research to design, conduct, and analyze interviews, and used simple frequencies to further describe findings. Results: Barriers to HCP coverage included poor fit with coverage frameworks (100%); insufficient evidence (100%); departure from pedigree/family history-based testing toward genetic screening (91%); lacking rigor in the HCP hybrid research/clinical setting (82%); and patient transparency and involvement concerns (82%). Addressing barriers requires refining HCP-indicated populations (82%); developing evidence of actionability (82%) and pathogenicity/penetrance (64%); creating infrastructure and standards for informing and recontacting patients (45%); separating research from clinical use in the hybrid clinical-research setting (44%); and adjusting coverage frameworks (18%). Conclusions: Leveraging opportunities suggested by payers to address HCP coverage barriers is essential to ensure patients' access to evolving HCPs. Our findings inform 3 areas of the PMI: addressing insurance coverage to secure access to future PMI discoveries; incorporating payers' evidentiary requirements into PMI's research agenda; and leveraging payers' recommendations and experience to keep patients informed and involved.

Racial/ethnic and socioeconomic differences in short-term breast cancer survival among women in an integrated health system.

OBJECTIVES: We examined the combined influence of race/ethnicity and neighborhood socioeconomic status (SES) on short-term survival among women with uniform access to health care and treatment. METHODS: Using electronic medical records data from Kaiser Permanente Northern California linked to data from the California Cancer Registry, we included 6262 women newly diagnosed with invasive breast cancer. We analyzed survival using multivariable Cox proportional hazards regression with follow-up through 2010. RESULTS: After consideration of tumor stage, subtype, comorbidity, and type of treatment received, non-Hispanic White women living in low-SES neighborhoods (hazard ratio [HR] = 1.28; 95% confidence interval [CI] = 1.07, 1.52) and African Americans regardless of neighborhood SES (high SES: HR = 1.44; 95% CI = 1.01, 2.07; low SES: HR = 1.88; 95% CI = 1.42, 2.50) had worse overall survival than did non-Hispanic White women living in high-SES neighborhoods. Results were similar for breast cancer-specific survival, except that African Americans and non-Hispanic Whites living in high-SES neighborhoods had similar survival. CONCLUSIONS: Strategies to address the underlying factors that may influence treatment intensity and adherence, such as comorbidities and logistical barriers, should be targeted at low-SES non-Hispanic White and all African American patients.

Patterns and predictors of breast cancer chemotherapy use in Kaiser Permanente Northern California, 2004-2007.

Chemotherapy regimens for early stage breast cancer have been tested by randomized clinical trials, and specified by evidence-based practice guidelines. However, little is known about the translation of trial results and guidelines to clinical practice. We extracted individual-level data on chemotherapy administration from the electronic medical records of Kaiser Permanente Northern California (KPNC), a pre-paid integrated healthcare system serving 29 % of the local population. We linked data to the California Cancer Registry, incorporating socio-demographic and tumor factors, and performed multivariable logistic regression analyses on the receipt of specific chemotherapy regimens. We identified 6,004 women diagnosed with Stage I-III breast cancer at KPNC during 2004-2007; 2,669 (44.5 %) received at least one chemotherapy infusion at KPNC within 12 months of diagnosis. Factors associated with receiving chemotherapy included <50 years of age [odds ratio (OR) 2.27, 95 % confidence interval (CI) 1.81-2.86], tumor >2 cm (OR 2.14, 95 % CI 1.75-2.61), involved lymph nodes (OR 11.3, 95 % CI 9.29-13.6), hormone receptor-negative (OR 6.94, 95 % CI 4.89-9.86), Her2/neu-positive (OR 2.71, 95 % CI 2.10-3.51), or high grade (OR 3.53, 95 % CI 2.77-4.49) tumors; comorbidities associated inversely with chemotherapy use [heart disease for anthracyclines (OR 0.24, 95 % CI 0.14-0.41), neuropathy for taxanes (OR 0.45, 95 % CI 0.22-0.89)]. Relative to high-socioeconomic status (SES) non-Hispanic Whites, we observed less anthracycline and taxane use by SES non-Hispanic Whites (OR 0.63, 95 % CI 0.49-0.82) and American Indians (OR 0.23, 95 % CI 0.06-0.93), and more anthracycline use by high-SES Asians/Pacific Islanders (OR 1.72, 95 % CI 1.02-2.90). In this equal-access healthcare system, chemotherapy use followed practice guidelines, but varied by race and socio-demographic factors. These findings may inform efforts to optimize quality in breast cancer care.