Association of a calcium channel blocker and diuretic prescribing cascade with adverse events: A population-based cohort study.

BACKGROUND: Prescribing cascades occur when a drug adverse event is misinterpreted as a new medical condition and a second, potentially unnecessary drug, is prescribed to treat the adverse event. The population-level consequences of prescribing cascades remain unknown. METHODS: This population-based cohort study used linked health administrative databases in Ontario, Canada. The study included community-dwelling adults, 66 years of age or older with hypertension and no history of heart failure (HF) or diuretic use in the prior year, newly dispensed a calcium channel blocker (CCB). Individuals subsequently dispensed a diuretic within 90 days of incident CCB dispensing were classified as the prescribing cascade group, and compared to those not dispensed a diuretic, classified as the non-prescribing cascade group. Those with and without a prescribing cascade were matched one-to-one on the propensity score and sex. The primary outcome was a serious adverse event (SAE), which was the composite of emergency room visits and hospitalizations in the 90-day follow-up period. We estimated hazard ratios (HRs) with 95% confidence intervals (CI) for SAE using an Andersen-Gill recurrent events regression model. RESULTS: Among 39,347 older adults with hypertension and no history of HF who were newly dispensed a CCB, 1881 (4.8%) had a new diuretic dispensed within 90 days after CCB initiation. Compared to the non-prescribing cascade group, those in the prescribing cascade group had higher rates of SAEs (HR: 1.21, 95% CI: 1.02-1.43). CONCLUSIONS: The CCB-diuretic prescribing cascade was associated with an increased rate of SAEs, suggesting harm beyond prescribing a second drug therapy. Our study raises awareness of the downstream impact of the CCB-diuretic prescribing cascade at a population level and provides an opportunity for clinicians who identify this prescribing cascade to review their patients' medications to determine if they can be optimized.

Risk of Breast Cancer After Diabetes in Pregnancy: A Population-based Cohort Study.

OBJECTIVES: Diabetes is associated with an increased risk of several cancers, including postmenopausal breast cancer. The evidence for higher breast cancer risk after diabetes in pregnancy is conflicting. We compared the incidence of breast and other cancers between pregnant women with and without diabetes. METHODS: This work was a propensity-matched, retrospective cohort study using population-based health-care databases from Ontario, Canada. Those deliveries with gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (pregestational DM) were identified and matched to deliveries without diabetes mellitus (non-DM). Deliveries from each diabetes cohort were matched 1:2 on age, parity, year of delivery, and propensity score to non-DM deliveries. Matched subjects were followed from delivery for incidence of breast cancer as a primary outcome, and other site-specific cancers as secondary outcomes. We performed Cox proportional hazards regression to compare rates of breast cancer between matched groups. RESULTS: Over a median of 8 (interquartile range 4 to 13) years of follow-up, compared with non-DM deliveries, the incidence of breast cancer was significantly lower for GDM but similar for pregestational DM deliveries (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.82 to 0.98; and HR 0.92, 95% CI 0.80 to 1.07, respectively). GDM was associated with a significantly higher incidence of pancreatic and hepatocellular cancer, and pregestational DM was associated with a higher incidence of thyroid, hepatocellular, and endometrial cancers. CONCLUSIONS: Diabetes in pregnancy does not have a higher short-term risk of subsequent breast cancer, but there may be a higher incidence of other cancers.

Physical Activity During Adolescence and Early-adulthood and Ovarian Cancer Among Women with a BRCA1 or BRCA2 Mutation.

In the general population, physical activity has been associated with a lower risk of several cancers; however, the evidence for ovarian cancer is not clear. It is suggested that early-life physical activity may differentially impact risk. Whether this is true among women at high risk due to a pathogenic variant (mutation) in the BRCA1 or BRCA2 genes has not been evaluated. Thus, we performed a matched case-control study to evaluate the association between adolescent and early-adulthood physical activity and ovarian cancer. BRCA mutation carriers who completed a research questionnaire on various exposures and incident disease and with data available on physical activity were eligible for inclusion. Self-reported activity at ages 12-13, 14-17, 18-22, 23-29, and 30-34 was used to calculate the average metabolic equivalent of task (MET)-hours/week for moderate, vigorous, and total physical activity during adolescence (ages 12-17) and early-adulthood (ages 18-34). Conditional logistic regression was used to estimate the OR and 95% confidence intervals (CI) of invasive ovarian cancer associated with physical activity. This study included 215 matched pairs (mean age = 57.3). There was no association between total physical activity during adolescence (ORhigh vs. low = 0.91; 95% CI: 0.61-1.36; Ptrend = 0.85), early-adulthood (ORhigh vs. low = 0.78; 95% CI: 0.51-1.20; Ptrend = 0.38) and overall (ORhigh vs. low = 0.81; 95% CI: 0.54-1.23; Ptrend = 0.56) and ovarian cancer. Findings were similar for moderate (Ptrend ≥ 0.25) and vigorous (Ptrend ≥ 0.57) activity. These findings do not provide evidence for an association between early-life physical activity and BRCA-ovarian cancer; however, physical activity should continue to be encouraged to promote overall health. SIGNIFICANCE: In this matched case-control study, we observed no association between physical activity during adolescence or early-adulthood and subsequent risk of ovarian cancer. These findings do not provide evidence for an association between early-life physical activity and BRCA-ovarian cancer; however, being active remains important to promote overall health and well-being.

Survival of Filipino women with breast cancer in the United States.

BACKGROUND: The survival of women with early-stage breast cancer varies by racial group. Filipino women with breast cancer are an understudied group and are often combined with other Asian groups. We compared clinical presentations and survival rates for Filipino and White women with breast cancer diagnosed in the United States. METHODS: We conducted a retrospective cohort study of women with breast cancer diagnosed between 2004 and 2015 in the SEER18 registries database. We compared crude survival between Filipino and White women. We then calculated adjusted hazard ratios (HR) in a propensity-matched design using the Cox proportional hazards model. RESULTS: There were 10,834 Filipino (2.5%) and 414,618 White women (97.5%) with Stage I-IV breast cancer in the SEER database. The mean age at diagnosis was 57.5 years for Filipino women and 60.8 years for White women (p < 0.0001). Filipino women had more high-grade and larger tumors than White women and were more likely to have node-positive disease. Among women with Stage I-IIIC breast cancer, the crude 10-year breast cancer-specific survival rate was 91.0% for Filipino and 88.9% for White women (HR 0.81, 95% CI 0.74-0.88, p < 0.01). In a propensity-matched analysis, the HR was 0.73 (95% CI 0.66-0.81). The survival advantage for Filipino women was present in subgroups defined by age of diagnosis, nodal status, estrogen receptor status, and HER2 receptor status. CONCLUSION: In the United States, Filipino women often present with more advanced breast cancers than White women, but experience better breast cancer-specific survival.

Salpingectomy and the Risk of Ovarian Cancer in Ontario.

Importance: A body of pathological and clinical evidence supports the position that the fallopian tube is the site of origin for a large proportion of high-grade serous ovarian cancers. Consequently, salpingectomy is now considered for permanent contraception (in lieu of tubal ligation) or ovarian cancer prevention (performed opportunistically at the time of surgical procedures for benign gynecologic conditions). Objective: To evaluate the association between salpingectomy and the risk of invasive epithelial ovarian, fallopian tube, and peritoneal cancer. Design, Setting, and Participants: This population-based retrospective cohort study included all women aged 18 to 80 years who were eligible for health care services in Ontario, Canada. Participants were identified using administrative health databases from Ontario between January 1, 1992, and December 31, 2019. A total of 131 516 women were included in the primary (matched) analysis. Women were followed up until December 31, 2021. Exposures: Salpingectomy (with and without hysterectomy) vs no pelvic procedure (control condition) among women in the general population. Main Outcomes and Measures: Women with a unilateral or bilateral salpingectomy in Ontario between April 1, 1992, and December 31, 2019, were matched 1:3 to women with no pelvic procedure from the general population. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% CIs for ovarian, fallopian tube, and peritoneal cancer combined. Results: Among 131 516 women (mean [SD] age, 42.2 [7.6] years), 32 879 underwent a unilateral or bilateral salpingectomy, and 98 637 did not undergo a pelvic procedure. After a mean (range) follow-up of 7.4 (0-29.2) years in the salpingectomy group and 7.5 (0-29.2) years in the nonsurgical control group, there were 31 incident cancers (0.09%) and 117 incident cancers (0.12%), respectively (HR, 0.82; 95% CI, 0.55-1.21). The HR for cancer incidence was 0.87 (95% CI, 0.53-1.44) when comparing those with salpingectomy vs those with hysterectomy alone. Conclusions and Relevance: In this cohort study, no association was found between salpingectomy and the risk of ovarian cancer; however, this observation was based on few incident cases and a relatively short follow-up time. Studies with additional years of follow-up are necessary to define the true level of potential risk reduction with salpingectomy, although longer follow-up will also be a challenge unless collaborative efforts that pool data are undertaken.

The association between immigration status and the development of type 2 diabetes in women with a prior diagnosis of gestational diabetes: A population-based study.

AIMS: The aim of this study was to examine the influence of immigration status and region of origin on the risk of type 2 diabetes in women with prior gestational diabetes (GDM). METHODS: This retrospective population-based cohort study included women with gestational diabetes (GDM) aged 16 to 50 years in Ontario, Canada, who gave birth between 2006 and 2014. We compared the incidence of type 2 diabetes after delivery between long-term residents and immigrants-overall, by time since immigration and by region of-using Cox regression adjusted for age, year, neighbourhood income, rurality, infant birth weight and presence of hypertensive disorders of pregnancy (HDP). RESULTS: Among 38,515 women with prior GDM (42% immigrants), immigrants had a significantly higher risk of type 2 diabetes compared with long-term residents (adjusted hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.13-1.26), with no meaningful difference based on time since immigration. The highest adjusted relative risks of type 2 diabetes compared with long-term residents were found for immigrants from Sub-Saharan Africa (HR 1.63, 95% CI 1.40-1.90), Latin America/Caribbean (HR 1.44, 95% CI 1.28-1.62) and South Asia (HR 1.34, 95% CI 1.25-1.44). CONCLUSIONS: Immigration is associated with a significantly higher risk of type 2 diabetes after GDM, particularly for women from certain low- and middle-income countries. Diabetes prevention strategies will need to consider the unique needs of immigrants from these regions.

The association between offspring birthweight and future risk of maternal diabetes: A population-based study.

AIMS: As an indicator of maternal cardiometabolic health, newborn birthweight may be an important predictor of maternal type 2 diabetes mellitus (diabetes). We evaluated the relation between offspring birthweight and onset of maternal diabetes after pregnancy. METHODS: This retrospective cohort study used linked population-based health databases from Ontario, Canada. We included women aged 16-50 years without pre-pregnancy diabetes, and who had a live birth between 2006 and 2014. We used Cox proportional hazard regression to evaluate the association between age- and sex-standardized offspring birthweight percentile categories and incident maternal diabetes, while adjusting for maternal age, parity, year, ethnicity, gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP). Results were further stratified by the presence of GDM in the index pregnancy. RESULTS: Of 893,777 eligible participants, 14,329 (1.6%) women were diagnosed with diabetes over a median (IQR) of 4.4 (1.5-7.4) years of follow-up. There was a continuous positive relation between newborn birthweight above the 75th percentile and maternal diabetes. Relative to a birthweight between the 50th and 74.9th percentiles, women whose newborn had a birthweight between the 97th and 100th percentiles had an adjusted hazards ratio (aHR) of diabetes of 2.30 (95% CI 2.16-2.46), including an aHR of 2.01 (95% CI 1.83-2.21) among those with GDM, and 2.59 (2.36-2.84) in those without GDM. CONCLUSIONS: A higher offspring birthweight signals an increased risk of maternal diabetes, offering another potentially useful way to identify women especially predisposed to diabetes.

Contemporary Trends in Breast Reconstruction Use and Impact on Survival Among Women with Inflammatory Breast Cancer.

BACKGROUND: Breast reconstruction is generally discouraged in women with inflammatory breast cancer (IBC). Nevertheless, reconstruction rates are increasing in this population. OBJECTIVE: We aimed to determine contemporary trends and predictors of breast reconstruction use and its impact on mortality among IBC patients. METHODS: Demographic, clinicopathologic, and follow-up data for women with non-metastatic IBC having mastectomy between 2004 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Rates and predictors of immediate breast reconstruction, along with survival outcomes between the breast reconstruction and no reconstruction groups were calculated. To account for selection bias, a propensity score analysis matching one reconstruction patient to three no reconstruction patients was performed. RESULTS: A total of 4076 women with non-metastatic IBC who underwent mastectomy (388 [9.5%] with breast reconstruction and 3688 [90.5%] without) were included. The proportion of women undergoing breast reconstruction and contralateral prophylactic mastectomy increased from 6.2 to 15.3% and 12.9 to 29.6%, respectively, between 2004 and 2015. Younger age, higher annual income, metropolitan residence, and bilateral mastectomy predicted breast reconstruction use. The 10-year breast cancer-specific survival was 62.9% for women having breast reconstruction and 47.6% for women not having breast reconstruction. After propensity-matched analysis, 10-year cancer-specific survival was similar between the reconstruction (56.6%) and no reconstruction (62.2%) groups (adjusted hazard ratio 0.96, 95% confidence interval 0.79-1.16; p = 0.65). CONCLUSIONS: Breast reconstruction rates continue to rise among IBC patients, particularly young women and women with access to reconstruction. Breast reconstruction is not associated with inferior breast cancer-specific survival and can be an option for select patients.

High Expression of RECQL Protein in ER-Positive Breast Tumours Is Associated With a Better Survival.

Background: RECQL (also known as RECQ1 and RECQL1) is a gene of recent interest in breast cancer and an association between high levels of RECQL protein in breast cancer tumour cells and good survival of patients has been reported. Methods: To validate this association, we measured the RECQL protein levels in tumours of 933 breast cancer patients using immunohistochemistry analysis and followed the patients for death from breast cancer. Results: Women with a level of RECQL protein above the 75th percentile had better 15-year disease-specific survival among ER-positive patients (62.5% vs. 48.7%, HR= 0.72, 95%CI= 0.52-0.98, p-value = 0.04), but not among ER- patients (48.9% vs. 48.0%, HR= 1.07, 95%CI= 0.67-1.69, p-value= 0.79). Among the ER-negative patients, high RECQL protein levels were associated with better survival among women who received tamoxifen treatment (67.0% vs. 51.5%, HR= 0.64, 95%CI= 0.41-0.99, p-value= 0.04). Conclusion: RECQL might be a new predictive marker for tamoxifen treatment among ER-positive patients.

Trends in platelet count among cancer patients.

An elevated platelet count has been associated with an increased incidence of cancer and poor survival for many cancer types. In this study, platelet levels were captured among cancer patients in the 2 years prior to and following a cancer diagnosis. I investigated if the trends in platelet count differ between patients that died or did not die from their cancer. For many cancer types, including colon, lung, ovary, and stomach, platelet counts rose as they approached the date of diagnosis. Patients that died from their cancer within 3 years of diagnosis had a higher peak platelet count than those who survived. Following diagnosis, platelet count was elevated among patients that died from their cancer as compared to patients who survived. An elevated platelet count could potentially indicate the presence of an occult cancer or be used as a prognostic measure for cancer-specific survival.

Platelet Count and Survival after Cancer.

Thrombocytosis is associated with cancer progression and death for many cancer types. It is unclear if platelet count is also associated with cancer survival. We conducted a cohort study of 112,231 adults in Ontario with a diagnosis of cancer between January 2007 and December 2016. We included patients who had a complete blood count (CBC) completed in the 30 days prior to their cancer diagnosis. Subjects were assigned to one of three categories according to platelet count: low (≤25th percentile), medium (>25 to <75th percentile), and high (≥75th percentile). Study subjects were followed from the date of their cancer diagnosis for cancer-specific death. Of the 112,231 eligible cancer patients in the cohort study, 40,329 (35.9%) died from their cancer in the follow-up period. Relative to those with a medium platelet count, the rate of cancer-specific death was higher among individuals with a high platelet count (HR 1.52; 95%CI 1.48-1.55) and was lower among individuals with a low platelet count (HR 0.91; 95%CI 0.88-0.93). A high platelet count was associated with poor survival for many cancer types. Platelet count could potentially be used as a risk stratification measure for cancer patients.

Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period.

Importance: Individuals with cancer often have an elevated platelet count at the time of diagnosis. The extent to which an elevated platelet count is an indicator of cancer is unclear. Objective: To evaluate the association of an elevated platelet count with a cancer diagnosis. Design, Setting, and Participants: This nested case-control study included Ontario residents enrolled in the provincial health insurance plan who had 1 or more routine complete blood count (CBC) tests performed between January 1, 2007, and December 31, 2017, with follow-up through December 31, 2018. Case patients were individuals with a new cancer diagnosis during the observation period. Eligible control individuals were cancer free before the date of diagnosis for a case patient to whom they were matched. One case patient was matched to 3 controls based on sex, age, and health care use patterns. Data were analyzed from September 24, 2020, to July 13, 2021. Exposures: Case patients and controls were assigned to 1 of 5 exposure groups based on age- and sex-specific platelet count distributions in the control population: very low (≤10th percentile), low (>10th to 25th percentile), medium (>25th to <75th percentile), high (75th to <90th percentile), and very high (≥90th percentile). Main Outcomes and Measures: Odds ratios (ORs) were estimated for specific cancer sites for each category of platelet count at intervals up to 10 years after a blood test. Results: Of the 8 917 187 eligible Ontario residents with a routine CBC record available, 4 971 578 (55.8%) were women; the median age at the first CBC was 46.4 years (IQR, 32.5-59.5 years). Among individuals with a routine CBC record available, 495 341 (5.6%) received a diagnosis of first primary cancer during the 10-year observation period. The OR for a solid tumor diagnosis associated with a very high platelet count vs a medium platelet count in the 6-month period before the diagnosis was 2.32 (95% CI, 2.28-2.35). A very high platelet count was associated with colon (OR, 4.38; 95% CI, 4.22-4.54), lung (OR, 4.37; 95% CI, 4.22-4.53), ovarian (OR, 4.62; 95% CI, 4.19-5.09), and stomach (OR, 4.27; 95% CI, 3.91-4.66) cancers. Odds ratios attenuated with increasing time from CBC test to cancer diagnosis. Conclusions and Relevance: In this nested case-control study, an elevated platelet count was associated with increased risk of cancer at several sites. Our findings suggest that an elevated platelet count could potentially serve as a marker for the presence of some cancer types.

Periodic screening for breast and cervical cancer in women with diabetes: a population-based cohort study.

PURPOSE: Diabetes is associated with poorer cancer outcomes. Screening for breast and cervical cancer is recommended by clinical guidelines; however, utilization of these tests in people with diabetes has been unclear due to methodological limitations in the evidence base. We used administrative data to determine the association between diabetes and the rates of becoming up-to-date with periodic breast and cervical cancer screening over a 20-year period. METHODS: Healthcare databases from Ontario, Canada, were linked to assemble two population-based cohorts of 50-70 and 21-70 year-olds between 1994 and 2011, eligible for breast and cervical cancer screening, respectively. Using age as the time scale, multivariable recurrent events models were implemented to examine the association between the presence of diabetes and the rates of becoming up-to-date with the recommended cancer screenings. RESULTS: In each of the breast and cervical cancer screening cohorts, there were, respectively, 1,516,302 (16% had diabetes at baseline) and 4,751,220 (9.5% had diabetes at baseline) screen-eligible women. In multivariable models, prevalent diabetes (duration ≥ 2 years) was associated with lower rates of becoming up-to-date with cervical (hazard ratio, HR 0.85, 95% confidence interval, CI 0.84-0.85) and breast (HR 0.94, CI 0.93-0.94) cancer screening, compared to no diabetes. CONCLUSIONS: Having diabetes is associated with decreased rates of becoming up-to-date with two recommended periodic cancer screenings, with a bigger reduction in the rates of becoming up-to-date with cervical cancer screening. Greater attention to cervical cancer preventive services is needed in women with diabetes.

Incidence of Cancer Among Adults With Thrombocytosis in Ontario, Canada.

Importance: Individuals with newly diagnosed cancer often have a high platelet count (thrombocytosis). Whether thrombocytosis is associated with the presence of an undiagnosed cancer remains unknown. Objective: To assess whether a new diagnosis of thrombocytosis is associated with a subsequent risk of cancer among adults. Design, Setting, and Participants: This population-based retrospective cohort study was conducted using linked laboratory data from Ontario, Canada, from January 1, 2007, to December 31, 2017, with follow-up until December 31, 2018. The study cohort included adults aged 40 to 75 years on the date of a routine complete blood count (CBC) test (index test) who had a normal platelet count in the 2 previous years and no history of cancer. Data analysis was performed in December 2020. Exposures: Exposed individuals were those with a platelet count greater than 450 × 109/L. Matched unexposed control individuals had a platelet count within the reference range (150 × 109/L to 450 × 109/L) reported within 30 days of the exposure. Main Outcomes and Measures: Incident cancers within 5 years after diagnosis of thrombocytosis. Absolute and relative risks for cancer associated with thrombocytosis were estimated for all cancers and for cancers at specific sites. Results: Of the 3 386 716 Ontario residents with a recorded routine CBC test result, 53 339 (1.6%) had thrombocytosis and a prior normal platelet count. Among individuals with thrombocytosis, the median age was 59.7 years (interquartile range, 50.2-67.4 years) and 37 349 (70.0%) were women. Among the 51 624 individuals with thrombocytosis included in the matched analysis, 2844 (5.5%) had received a diagnosis of a solid cancer in the 2-year follow-up period and 3869 (7.5%) had received a diagnosis within 5 years. The relative risk (RR) for developing any solid cancer within 2 years was 2.67 (95% CI, 2.56-2.79). Associations were found between thrombocytosis and cancers of the ovary (RR, 7.11; 95% CI, 5.59-9.03), stomach (RR, 5.53; 95% CI, 4.12-7.41), colon (RR, 5.41; 95% CI, 4.80-6.10), lung (RR, 4.41; 95% CI, 4.02-4.85), kidney (RR, 3.64; 95% CI, 2.94-4.51), and esophagus (RR, 3.64; 95% CI, 2.46-5.40). Conclusions and Relevance: In this cohort study, an increased platelet count was associated with an increased risk of cancer for at least 2 years. The results suggest that individuals with unexplained thrombocytosis should be offered screening for several cancers.

Evidence of a gabapentinoid and diuretic prescribing cascade among older adults with lower back pain.

BACKGROUND/OBJECTIVES: Gabapentinoids are commonly prescribed to relieve pain. The development of edema, an established adverse effect of gabapentinoids, may lead to a potentially harmful prescribing cascade whereby individuals are subsequently prescribed diuretics and exposed to diuretic-induced adverse events. The frequency of this prescribing cascade is unknown. Our objective was to measure the association between new dispensing of a gabapentinoid and the subsequent dispensing of a diuretic in older adults with new low back pain. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: A total of 260,344 community-dwelling adults aged 66 years or older, newly diagnosed with low back pain between April 1, 2011, and March 31, 2019. MEASUREMENTS: Exposure status was assigned using dispensed medications in the 1 week after low back pain diagnosis. Older adults newly dispensed a gabapentinoid (N = 7867) were compared with older adults who were not newly dispensed a gabapentinoid (N = 252,477). Hazard ratios (HRs) with 95% confidence intervals (CIs) for dispensing of a diuretic within 90 days of follow-up among older adults prescribed gabapentin relative to those who were not. RESULTS: Older adults newly dispensed a gabapentinoid had a higher risk of being subsequently dispensed a diuretic within 90 days compared with older adults who were not prescribed a gabapentinoid (2.0% vs. 1.3%). After covariate adjustment, new gabapentinoid users had a higher rate of being dispensed a diuretic compared with those not prescribed a gabapentinoid (HR: 1.44, 95% CI: 1.23, 1.70). The rate of diuretic prescription among new gabapentinoid users increased with increasing gabapentinoid dosages. CONCLUSIONS: We have demonstrated the presence of a potentially inappropriate and harmful prescribing cascade. Given the widespread use of gabapentinoids, the population-based scale of this problem may be substantial. Increased awareness of this prescribing cascade is required to reduce the unnecessary use of diuretics and the exposure of patients to additional adverse drug events.

The risk of contralateral breast cancer: a SEER-based analysis.

BACKGROUND: We sought to estimate the annual risk and 25-year cumulative risk of contralateral breast cancer among women with stage 0-III unilateral breast cancer. METHODS: We identified 812,851 women with unilateral breast cancer diagnosed between 1990 and 2015 in the SEER database and followed them for contralateral breast cancer for up to 25 years. Women with a known bilateral mastectomy were excluded. We calculated the annual risk of contralateral breast cancer by age at diagnosis, by time since diagnosis and by current age. We compared risks by ductal carcinoma in situ (DCIS) versus invasive disease, by race and by oestrogen receptor (ER) status of the first cancer. RESULTS: There were 25,958 cases of contralateral invasive breast cancer diagnosed (3.2% of all patients). The annual risk of contralateral breast cancer over the 25-year follow-up period was 0.37% and the 25-year actuarial risk of contralateral invasive breast cancer was 9.9%. The annual risk varied to a small degree by age of diagnosis, by time elapsed since diagnosis and by current age. The 25-year actuarial risk was similar for DCIS and invasive breast cancer patients (10.1 versus 9.9%). The 25-year actuarial risk was higher for black women (12.7%) than for white women (9.7%) and was lower for women with ER-positive breast cancer (9.5%) than for women with ER-negative breast cancer (11.2%). CONCLUSIONS: Women with unilateral breast cancer experience an annual risk of contralateral breast cancer ~0.4% per year, which persists over the 25-year follow-up period.

The relationship between the predicted risk of death and psychosocial functioning among women with early-stage breast cancer.

PURPOSE: Many women with early-onset breast cancer experience adverse psychological sequelae which impact on their quality of life. We sought to correlate levels of anxiety and cancer-related distress in women with breast cancer shortly after surgery and one year after treatment with the estimated risk of death. METHODS: We studied 596 women with Stage I to III breast cancer. For each woman we estimated the five-year risk of death based on SEER data from 2010 to 2019. For each woman we measured anxiety and cancer-related distress levels shortly after surgery and one year later. RESULTS: The mean estimated five-year survival was 95%. At one week post-surgery, 59% of women had a clinically significant level of anxiety and 74% had a clinically significant level of cancer-related distress. There was no correlation between the objective risk of death and the level of anxiety or distress, at one week or at one year. CONCLUSIONS: Many women diagnosed with early-stage breast cancers experience significant levels of anxiety and distress. The emotional response to a breast cancer diagnosis is not related to the risk of death per se and other factors should be explored.