Adjuvant Hormone Therapy-Related Hot Flashes Predict Treatment Discontinuation and Worse Breast Cancer Prognosis.

BACKGROUND: Clinical trials have shown that adjuvant hormone therapy (AHT)-related hot flashes can predict better breast cancer outcomes. This population-based cohort study investigated whether this result can be generalized to a real-world setting. PATIENTS AND METHODS: By linking the National Quality Registry for Breast Cancer, Prescribed Drug Register, and Cause-of-Death Register, we identified 7,152 chemotherapy-free patients with breast cancer who initiated AHT in Stockholm from 2006 through 2019, and followed them until 2020. Hot flashes were defined as new use of drugs for hot flashes within 6 months after initiating AHT. We used Cox models to compare disease-free survival and treatment discontinuation among patients with and without hot flashes. RESULTS: Patients who newly used drugs for hot flashes shortly after AHT initiation had worse disease-free survival (adjusted hazard ratio [HR], 1.67; 95% CI, 1.11-2.52) and a higher treatment discontinuation rate (adjusted HR, 1.47; 95% CI, 1.21-1.78). The association between drugs for hot flashes and discontinuation of AHT differed by patient characteristics, with stronger associations among low-income patients (HR, 1.91; 95% CI, 1.41-2.59) and those without first-degree relatives who had cancer (HR, 1.81; 95% CI, 1.39-2.35) or died from cancer (HR, 1.71; 95% CI, 1.37-2.12). CONCLUSIONS: AHT-related hot flashes predict worse, rather than better, breast cancer outcomes among patients in clinical routine practice. The identification of adverse effects by the initiation of hot flash medications may identify a subset of patients with more severe hot flashes who are more likely to discontinue AHT and need more support for treatment adherence.

Familial adversity: association with discontinuation of adjuvant hormone therapy and breast cancer prognosis.

BACKGROUND: Many studies have examined patient-related factors affecting adjuvant hormone therapy adherence in patients with breast cancer. Our study aimed to examine associations of family-related factors with adjuvant hormone therapy discontinuation and breast cancer-specific mortality. METHODS: By cross-linking 7 Swedish health registers, we performed a cohort study that included all patients with breast cancer who initiated adjuvant hormone therapy during 2006-2019 in Sweden (N = 10 701). A group-based multitrajectory model was used to identify familial adversity groups based on 3 dimensions: material deprivation, negative family dynamics, and loss or threat of loss. Cox proportional hazard models were used to investigate associations of familial adversity with hormone therapy discontinuation and breast cancer-specific mortality. RESULTS: We identified 5 distinctive familial adversity groups among the cohort participants. Compared with women who had low familial adversity, higher risks to discontinue adjuvant hormone therapy were observed among women with material deprivation (hazard ratio [HR] = 1.31, 95% confidence interval [CI] = 1.20 to 1.43), negative family dynamics (HR = 1.16, 95% CI = 1.06 to 1.28), loss or threat of loss (HR = 1.15, 95% CI = 1.00 to 1.32), or high familial adversity (HR = 1.53, 95% CI = 1.40 to 1.68). Furthermore, women with material deprivation (HR = 1.37, 95% CI = 1.05 to 1.79), negative family dynamics (HR = 1.41, 95% CI = 1.01 to 1.97), or high adversity (HR = 1.67, 95% CI = 1.26 to 2.23) were at higher risk of dying from breast cancer. CONCLUSION: Familial adversity is associated with a higher risk of adjuvant hormone therapy discontinuation and breast cancer-specific mortality. Family-related factors identified in our study may help identify high-risk patients for interventions to prevent treatment discontinuation and subsequently improve breast cancer outcomes.

Concomitant Discontinuation of Cardiovascular Therapy and Adjuvant Hormone Therapy Among Patients With Breast Cancer.

Importance: A large proportion of patients with breast cancer concomitantly use adjuvant hormone therapy and cardiovascular therapy. Objective: To examine the relative risk of discontinuing cardiovascular therapy during the periods before and after discontinuation of adjuvant hormone therapy. Design, Setting, and Participants: This population-based cohort study included all women aged 40 to 74 years in Stockholm, Sweden, who were diagnosed with breast cancer and concomitantly using adjuvant hormone therapy and cardiovascular therapy. Patients were enrolled from July 1, 2005, to August 31, 2020, with a median follow-up of 7.2 years. Data were analyzed from November 3, 2021, to May 12, 2022. Exposure: Discontinuation of adjuvant hormone therapy. Main Outcomes and Measures: The main outcome was discontinuation of cardiovascular therapy (cardiovascular drugs, statins, or aspirin) within 1 year before and after discontinuation of adjuvant hormone therapy. Incidence rate ratios with 95% CIs were estimated using Poisson regression. Furthermore, hazard ratios (HRs) with 95% CIs for cause-specific mortality were estimated using Cox proportional hazards regression models, comparing those who discontinued and continued adjuvant hormone therapy. Results: A total of 5493 patients with breast cancer who concomitantly used cardiovascular therapy were identified; 1811 who discontinued adjuvant hormone therapy were individually matched to 1 patient each who continued therapy by year of breast cancer diagnosis, age at diagnosis, and use of the same cardiovascular therapy. Most patients (4070 [74.1%]) were aged 60 years or older at diagnosis. At the time when patients discontinued adjuvant hormone therapy, 248 (12.2%) concomitantly discontinued their cardiovascular therapy. During follow-up, a higher discontinuation rate of cardiovascular therapy was also observed among those who discontinued adjuvant hormone therapy. Consistently, adjuvant hormone therapy discontinuation was associated with an increased risk of death not only due to breast cancer (HR, 1.43; 95 CI%, 1.01-2.01) but also cardiovascular disease (HR, 1.79; 95 CI%, 1.15-2.81). Stratifying the analyses on baseline type of adjuvant hormone therapy yielded consistent results. Conclusions and Relevance: In this cohort study of data from population-based registers in Sweden, patients who discontinued adjuvant hormone therapy were also more likely to discontinue cardiovascular therapy, especially at the time when they discontinued adjuvant hormone therapy. These findings suggest that clinicians should shift from single- to multiple-disease focus to prevent discontinuation of therapies for other diseases among patients with breast cancer.

Analysis of Breast Cancer Family History, Estrogen Receptor Status, and Breast Cancer Outcomes in Sweden.

Importance: Breast cancer (BC), the most prevalent cancer among women globally, is a heterogeneous disease, with prognosis differing by estrogen receptor (ER) status. Having a family history of BC increases the risk of BC; however, it is unclear whether family history is associated with the prognosis of overall and ER-specific BC. Objective: To assess whether a family history of BC is associated with the prognosis of overall and ER-specific BC. Design, Setting, and Participants: This cohort study was based on data from several national registers in Sweden. All female residents of Stockholm who were born after 1932; had their first BC diagnosis between January 1, 1991, and December 31, 2019; and had at least 1 identified female first-degree relative (FDR) were included. Women who were diagnosed with other types of cancer before their BC diagnosis, were older than 75 years at diagnosis, or had distant metastasis at diagnosis were excluded. A total of 28 649 women were included. Data were analyzed from January 10, 2022, to December 20, 2022. Exposures: Family history of BC, defined as 1 or more female FDRs diagnosed with BC. Main Outcomes and Measures: Patients were followed up until BC-specific death, censoring, or end of follow-up on December 31, 2019. The role of family history in BC-specific mortality was investigated using flexible parametric survival models among the full cohort, ER-positive subgroup, and ER-negative subgroup, adjusting for demographic characteristics, tumor characteristics, and treatments received. Results: Among 28 649 patients, the mean (SD) age at BC diagnosis was 55.7 (10.4) years; 19 545 (68.2%) had ER-positive BC, and 4078 (14.2%) had ER-negative BC. Overall, 5081 patients (17.7%) had at least 1 female FDR diagnosed with BC, while 384 (1.3%) had a family history of early-onset BC (FDR diagnosed before age 40 years). During the follow-up period (median [IQR], 8.7 [4.1-15.1] years), 2748 patients (9.6%) died of BC. Multivariable analyses revealed that having a family history of BC was associated with a lower risk of BC-specific death among the full cohort (hazard ratio [HR], 0.78; 95% CI, 0.65-0.95) and the ER-negative subgroup (HR, 0.57; 95% CI, 0.40-0.82) in the first 5 years, after which no association was observed. However, having an early-onset family history was associated with a higher risk of BC-specific death (HR, 1.41; 95% CI, 1.03-2.34). Conclusions and Relevance: In this study, patients with a family history of BC did not necessarily have a worse prognosis. Those with ER-negative status and a family history of BC had more favorable outcomes in the first 5 years after diagnosis, possibly due to enhanced motivation to receive and adhere to treatment. However, patients with a family history of early-onset BC had worse survival, suggesting that genetic testing of newly diagnosed patients with early-onset family history may provide useful information to aid treatment and future research.

Risk of estrogen receptor-specific breast cancer by family history of estrogen receptor subtypes and other cancers.

BACKGROUND: The extent to which the risk of estrogen receptor (ER)-specific breast cancer is associated with ER status of breast cancer and other cancers among first-degree relatives is unclear. METHODS: This population-based cohort included 464 707 cancer-free women in Stockholm, Sweden, during 1978-2019. For ER-negative and ER-positive breast cancers, we estimated hazard ratios (HRs) associated with ER status of female first-degree relatives with breast cancer and of other cancers in all first-degree relatives. Associations between ER-negative and ER-positive status by family cancer history were estimated using logistic regression in a case-only design. RESULTS: Women with familial ER-positive breast cancer had 1.87 times (95% confidence interval [CI] = 1.77 to 1.97) higher risk of ER-positive subtype, whereas the corresponding hazard ratio for ER-negative was 2.54 (95% CI = 2.08 to 3.10) when having familial ER-negative breast cancer. The risk increased with an increasing number of female first-degree relatives having concordant subtypes and younger age at diagnosis (Ptrend <.001 for both). Nonbreast cancers among first-degree relatives were associated with both ER-positive (HR = 1.14, 95% CI = 1.10 to 1.17) and ER-negative (HR = 1.08, 95% CI = 1.01 to 1.16) breast cancers. Compared with women with ER-positive breast cancer, women with ER-negative breast cancer were more likely to have family history of liver (odds ratio [OR] = 1.33, 95% CI = 1.05 to 1.67), ovary (OR = 1.28, 95% CI = 1.01 to 1.61), and testicle cancer (OR = 1.79, 95% CI = 1.01 to 3.16) but less likely to have family history of endometrial cancer (OR = 0.77, 95% CI = 0.60 to 1.00) and leukemia (OR = 0.72, 95% CI = 0.56 to 0.91). CONCLUSIONS: Risk of ER-specific breast cancer differs according to ER status of female first-degree relatives with breast cancer and some other cancers of first-degree relatives. This family history information should be considered in the individual risk prediction for ER subtypes.

Determinants and Effectiveness of Extending the Duration of Adjuvant Hormone Therapy beyond 5 Years in Patients with Breast Cancer.

Clinical guidelines have recommended patients with high-risk breast cancer to extend adjuvant hormone therapy beyond 5 years. However, the prevalence, predictors, and outcomes of extended adjuvant hormone therapy in the real world remain unknown. By linking six Swedish health registries, we prospectively followed 13,168 patients with breast cancer (2005-2020) from their first prescription of tamoxifen or aromatase inhibitors and categorized them as extending or not extending adjuvant hormone therapy. Cox regression analysis was used to investigate whether extended therapy was associated with breast cancer outcomes. Among patients with breast cancer who were recommended to extend adjuvant hormone therapy by the national guidelines, the proportion of women who extended therapy increased 5 folds during the past 10 years, reaching 80.9% during 2018 to 2020. Patients were more likely to extend therapy after completing 5-year adjuvant hormone therapy if they were young [40 vs. ≥65 years: OR, 1.71; 95% confidence interval (CI), 1.13-2.58], had positive lymph nodes (OR, 2.25; 95% CI, 1.85-2.73), had high tumor grade (grade 3 vs. 1: OR, 1.79; 95% CI, 1.34-2.39), received chemotherapy (OR, 5.22; 95% CI, 4.19-6.50), had first-degree relatives who died from breast cancer (OR, 1.84; 95% CI, 1.21-2.81), or had a high income (OR, 1.23; 95% CI, 1.01-1.49). Extended use of adjuvant hormone therapy was statistically significantly associated with improved disease-free survival (HR, 0.72; 95 CI%, 0.55-0.95). This study provides real-world evidence showing the use and improved breast cancer outcomes of extended adjuvant hormone therapy beyond 5 years. SIGNIFICANCE: The proportion of patients with breast cancer extending adjuvant hormone therapy beyond 5 years has increased dramatically in recent years, which is associated with improved patient outcomes.

Risk of heart disease following treatment for breast cancer - results from a population-based cohort study.

Background: There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure, and ischemic heart disease in women diagnosed with breast cancer. Methods: A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region and followed up until 2017. Time-dependent risks of arrhythmia, heart failure, and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model. Results: Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR = 1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following locoregional radiotherapy. Conclusions: Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices. Funding: This work was supported by the Swedish Research Council (grant no: 2018-02547); Swedish Cancer Society (grant no: CAN-19-0266); and FORTE (grant no: 2016-00081).