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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. [ABSTRACT FROM AUTHOR]

Background: Treatment of cervical intraepithelial neoplasia grade 3 (CIN 3) removes or destroys part of the cervix and might subsequently influence pregnancy outcomes.Objective: To investigate pregnancy outcomes in women diagnosed with CIN 3.Design: Population- and sibling-matched cohort study.Setting: Sweden, 1973 to 2018.Participants: The general population comparison included 78 450 singletons born to women diagnosed with CIN 3 and 784 500 matched singletons born to women in the general population who had no CIN 3 diagnosis; the sibling comparison included 23 199 singletons born to women diagnosed with CIN 3 and 28 135 singletons born to their sisters without a CIN 3 diagnosis.Measurements: Preterm birth, including spontaneous or iatrogenic preterm birth; infection-related outcomes, including chorioamnionitis and infant sepsis; and early neonatal death, defined as death during the first week after birth.Results: Compared with the matched general population, women previously diagnosed with CIN 3 were more likely to have a preterm birth, especially extremely preterm (22 to 28 weeks; odds ratio [OR], 3.00 [95% CI, 2.69 to 3.34]) or spontaneous preterm (OR, 2.12 [CI, 2.05 to 2.20]); infection-related outcomes, including chorioamnionitis (OR, 3.23 [CI, 2.89 to 3.62]) and infant sepsis (OR, 1.72 [CI, 1.60 to 1.86]); or early neonatal death (OR, 1.83 [CI, 1.61 to 2.09]). Sibling comparison analyses rendered largely similar results. Over time, the risk difference attenuated for all outcomes and disappeared for early neonatal death.Limitation: Lack of data on CIN 3 treatment and spontaneous abortion.Conclusion: History of CIN 3 is associated with adverse pregnancy outcomes even after accounting for familial factors. Decreasing risk estimates over time suggest that adverse pregnancy outcomes among women diagnosed with CIN 3 may be minimized by improving treatment methods.Primary Funding Source: The Swedish Research Council, the Swedish Cancer Society, and the Swedish Research Council for Health, Working Life and Welfare. [ABSTRACT FROM AUTHOR]

Background: Over half of breast cancer patients discontinue their adjuvant hormone therapy, permanently or temporarily. We aimed to identify predictors of treatment restarting after discontinuation of adjuvant hormone therapy and to test the hypothesis that treatment restarting is associated with better breast cancer outcomes.Methods: We conducted a population-based cohort study by linking data from the Stockholm-Gotland Breast Cancer Register, the Swedish Prescribed Drug Register, and a self-reported questionnaire. We followed women diagnosed with breast cancer (Stockholm, Sweden, 2005-2008) from their first prescription of tamoxifen or aromatase inhibitors through January 31, 2015, and categorized them as continuers (n = 1 607), restarters (n = 953), and nonrestarters (n = 511) of adjuvant hormone therapy. All statistical tests were two-sided.Results: Factors that decrease the likelihood of treatment restarting included younger age (<50 years), higher Charlson Comorbidity Score (≥2), smaller tumor size (<20 mm), human epidermal growth factor receptor 2 negative, lymph node negative, family history of breast cancer negative, using hormone therapy, using symptom relieving drugs, and switching therapy between tamoxifen and aromatase inhibitors. Restarting adjuvant hormone therapy was statistically significantly associated with prolonged disease-free survival, with an adjusted hazard ratio of 0.61 (95% confidence interval = 0.43 to 0.87, P = .006) for restarters vs nonrestarters.Conclusions: Our study provides-for the first time to our knowledge-evidence that restarting adjuvant hormone therapy is associated with better breast cancer outcomes. Clinicians now have further evidence to encourage patients to restart their treatment after discontinuation of adjuvant hormone therapy. [ABSTRACT FROM AUTHOR]

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.

Mammographic features influence breast cancer risk and are used in risk prediction models. Understanding how genetics influence mammographic features is important because the mechanisms through which they are associated with breast cancer are not well known. Here, using mammographic screening history and detailed questionnaire data from 56,820 women from the KARMA prospective cohort study, we investigated the association between a genetic predisposition to breast cancer and mammographic features among women with a family history of breast cancer ( N = 49,674) and a polygenic risk score (PRS, N = 9,365). The heritability of mammographic features such as dense area (MD), microcalcifications, masses, and density change (MDC, cm 2 /year) was estimated using 1,940 sister pairs. Heritability was estimated at 58% [95% confidence interval (CI), 48%-67%) for MD, 23% (2%-45%) for microcalcifications, and 13% (1%-25%)] for masses. The estimated heritability for MDC was essentially null (2%; 95% CI, -8% to 12%). The association between a genetic predisposition to breast cancer (using PRS) and MD and microcalcifications was positive, while for masses this was borderline significant. In addition, for MDC, having a family history of breast cancer was associated with slightly greater MD reduction. In summary, we have confirmed previous findings of heritability in MD, and also established heritability of the number of microcalcifications and masses at baseline. Because these features are associated with breast cancer risk and can improve detecting women at short-term risk of breast cancer, further investigation of common loci associated with mammographic features is warranted to better understand the etiology of breast cancer. SIGNIFICANCE: These findings provide novel data on the heritability of microcalcifications, masses, and density change, which are all associated with breast cancer risk and can indicate women at short-term risk., (©2020 American Association for Cancer Research.)

Breast cancer (BC) patients diagnosed between two screenings (interval cancers) are more likely than screen-detected patients to carry rare deleterious mutations in cancer genes potentially leading to increased risk for other non-breast cancer (non-BC) tumors. In this study, we include 14,846 women diagnosed with BC of which 1,772 are interval and 13,074 screen-detected. Compared to women with screen-detected cancers, interval breast cancer patients are more likely to have a non-BC tumor before (Odds ratio (OR): 1.43 [1.19-1.70], P = 9.4 x 10 -5 ) and after (OR: 1.28 [1.14-1.44], P = 4.70 x 10 -5 ) breast cancer diagnosis, are more likely to report a family history of non-BC tumors and have a lower genetic risk score based on common variants for non-BC tumors. In conclusion, interval breast cancer is associated with other tumors and common cancer variants are unlikely to be responsible for this association. These findings could have implications for future screening and prevention programs.

Purpose: Breast cancer is a common disease with a relatively good prognosis. Therefore, understanding the spectrum of diseases and mortality among breast cancer patients is important, though currently incomplete. We systematically examined the incidence and mortality of all diseases following a breast cancer diagnosis, as well as the sequential association of disease occurrences (trajectories)., Methods: In this national cohort study, 57,501 breast cancer patients (2001-2011) were compared to 564,703 matched women from the general Swedish population and followed until 2012. The matching criteria included year of birth, county of residence, and socioeconomic status. Based on information from the Swedish Patient and Cause of Death Registries, hazard ratios (HR) were estimated for disease incidence and mortality. Conditional logistic regression models were used to identify disease trajectories among breast cancer patients., Results: Among 225 diseases, 45 had HRs > 1.5 and p < 0.0002 when comparing breast cancer patients with the general population. Diseases with highest HRs included lymphedema, radiodermatitis, and neutropenia, which are side effects of surgery, radiotherapy, and chemotherapy. Other than breast cancer, the only significantly increased cause of death was other solid cancers (HR = 1.16, 95% CI = 1.08-1.24). Two main groups of disease trajectories were identified, which suggest menopausal disorders as indicators for other solid cancers, and both neutropenia and dorsalgia as diseases and symptoms preceding death due to breast cancer., Conclusions: While an increased incidence of other diseases was found among breast cancer patients, increased mortality was only due to other solid cancers. Preventing death due to breast cancer should be a priority to prolong life in breast cancer patients, but closer surveillance of other solid cancers is also needed.

Background: Breast cancer patients who have not previously attended mammography screening may be more likely to discontinue adjuvant hormone therapy and therefore have a worse disease prognosis., Methods: We conducted a population-based cohort study using data from Stockholm Mammography Screening Program, Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and Swedish Cause of Death Register. Women in Stockholm who were diagnosed with breast cancer between 2001 and 2008 were followed until December 31, 2015. Non-participants of mammography screening were defined as women who, prior to their breast cancer diagnosis, were invited for mammography screening but did not attend., Results: Of the 5098 eligible breast cancer patients, 4156 were defined as screening participants and 942 as non-participants. Compared with mammography screening participants, non-participants were more likely to discontinue adjuvant hormone therapy, with an adjusted hazard ratio (HR) of 1.30 (95% CIs, 1.11 to 1.53). Breast cancer patients not participating in mammography screening were also more likely to have worse disease-free survival, even after adjusting for tumor characteristics and other covariates (adjusted HR 1.22 (95% CIs, 1.05 to 1.42 for a breast cancer event)., Conclusions: Targeted interventions to prevent discontinuation of adjuvant hormone therapy are needed to improve breast cancer outcomes among women not attending mammography screening.

Background: Preeclampsia is frequently linked to reduced breast cancer risk. However, little is known regarding the underlying genetic association and the association between preeclampsia and mammographic density., Methods: This study estimates the incidence rate ratios (IRRs) of breast cancer in patients with preeclampsia, when compared to women without preeclampsia, using Poisson regression models in two cohorts of pregnant women: a Swedish nationwide cohort (n = 1,337,934, 1973-2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 55,044, 1958-2015). To identify the genetic association between preeclampsia and breast cancer, we used logistic regression models to calculate the odds ratios (ORs) of preeclampsia in sisters of breast cancer patients, and in women with different percentiles of breast cancer polygenic risk scores (PRS). Linear regression models were used to estimate the mammographic density by preeclampsia status in the KARMA cohort., Results: A decreased risk of breast cancer was observed among patients with preeclampsia in both the nationwide (IRR = 0.90, 95% CI = 0.85; 0.96) and KARMA cohorts (IRR = 0.75, 95% CI = 0.61; 0.93). Women with high breast cancer PRS and sisters of breast cancer patients had a lower risk of preeclampsia (OR = 0.89, 95% CI = 0.83; 0.96). Mammographic density was lower in women with preeclampsia compared to women without preeclampsia (-2.04%, 95% CI = -2.65; -1.43). Additionally, among sisters in the KARMA cohort (N = 3500), density was lower in sisters of patients with preeclampsia compared to sisters of women without preeclampsia (-2.76%, 95% CI = -4.96; -0.56)., Conclusion: Preeclampsia is associated with reduced risk of breast cancer and mammographic density. Inherited factors contribute to this inverse association.

Large childhood body size has been consistently shown to be associated with decreased breast cancer risk. However, it is important to consider the effects of a large childhood body size on other adult diseases. It is not clear if the associations between childhood body size and adult diseases will persist if they later attain healthy weight. The associations between body size at age 7 and 17 adverse outcomes in adulthood were examined using Cox models in a Swedish study of 65,057 women. Large body size at age 7, when compared to small body size, was associated with decreased risk for breast cancer (HR [95% CI]: 0.81 [0.70-0.93]) and increased risks for anorexia (2.13 [1.63-2.77]) and bulimia (1.91 [1.35-2.70]). Neither adjusting for adult BMI nor restricting the dataset to lean adults (BMI < 25 kg/m 2 ) attenuated the associations. While large body size at age 7 by itself was positively associated with increased risks of diabetes (1.34 [1.16-1.55]), PCOS (1.69 [1.13-2.51]) and hypertension (before age 60), the associations were no longer significant after controlling for adult BMI. No clear associations were found with the remaining adverse outcomes (cervical, uterine, melanoma, colon cancer, depression, ovarian cyst, stroke, hyperlipidemia, heart failure, myocardial infarction, and angina pectoris).

Background: Over half of breast cancer patients discontinue their adjuvant hormone therapy, permanently or temporarily. We aimed to identify predictors of treatment restarting after discontinuation of adjuvant hormone therapy and to test the hypothesis that treatment restarting is associated with better breast cancer outcomes., Methods: We conducted a population-based cohort study by linking data from the Stockholm-Gotland Breast Cancer Register, the Swedish Prescribed Drug Register, and a self-reported questionnaire. We followed women diagnosed with breast cancer (Stockholm, Sweden, 2005-2008) from their first prescription of tamoxifen or aromatase inhibitors through January 31, 2015, and categorized them as continuers (n = 1 607), restarters (n = 953), and nonrestarters (n = 511) of adjuvant hormone therapy. All statistical tests were two-sided., Results: Factors that decrease the likelihood of treatment restarting included younger age (<50 years), higher Charlson Comorbidity Score (≥2), smaller tumor size (<20 mm), human epidermal growth factor receptor 2 negative, lymph node negative, family history of breast cancer negative, using hormone therapy, using symptom relieving drugs, and switching therapy between tamoxifen and aromatase inhibitors. Restarting adjuvant hormone therapy was statistically significantly associated with prolonged disease-free survival, with an adjusted hazard ratio of 0.61 (95% confidence interval = 0.43 to 0.87, P = .006) for restarters vs nonrestarters., Conclusions: Our study provides-for the first time to our knowledge-evidence that restarting adjuvant hormone therapy is associated with better breast cancer outcomes. Clinicians now have further evidence to encourage patients to restart their treatment after discontinuation of adjuvant hormone therapy., (© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To identify predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer., Patients and Methods: We conducted a record-linkage study based on data from Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and self-reported questionnaire. Women diagnosed with breast cancer between 2005 and 2008 in Stockholm, Sweden, were prospectively followed for 5 years until 2013, starting from their first prescription of tamoxifen or aromatase inhibitors (N = 3,395)., Results: Family history of ovarian cancer (hazard ratio [HR], 1.55; 95% CI, 1.19 to 2.02); younger (< 40 years; HR, 1.39; 95% CI, 1.08 to 1.78) and older (≥ 65 years; HR, 1.15; 95% CI, 1.03 to 1.28) age; higher Charlson comorbidity index (≥ 2 v 0; HR, 1.35; 95% CI, 1.03 to 1.76); and use of analgesics (HR, 1.33; 95% CI, 1.16 to 1.52), hypnotics/sedatives (HR, 1.24; 95% CI, 1.07 to 1.43), GI drugs (HR, 1.25; 95% CI, 1.08 to 1.43), and hormone replacement therapy (HR, 1.27; 95% CI, 1.08 to 1.49) were identified as baseline predictors for hormonal treatment discontinuation. Use of analgesics (HR, 1.22; 95% CI, 1.08 to 1.37), hypnotics/sedatives (HR, 1.21; 95% CI, 1.07 to 1.37), antidepressants (HR, 1.22; 95% CI, 1.06 to 1.40), or GI drugs (HR, 1.27; 95% CI, 1.13 to 1.43), and switching therapy between tamoxifen and aromatase inhibitors (HR, 1.50; 95% CI, 1.23 to 1.83) during the first year of hormonal treatment were associated with increased risk of discontinuation during the next 4 years., Conclusion: Predictors identified in our study can be used in developing targeted intervention to prevent adjuvant hormone therapy discontinuation and subsequently to improve breast cancer outcomes., (© 2015 by American Society of Clinical Oncology.)