Higher Breast Cancer-specific Mortality Research Articles

Increased breast cancer mortality due to treatment delay and needle biopsy type: a retrospective analysis of SEER-medicare

BackgroundSubstantial evidence indicates that delay of first treatment after diagnosis is associated with poorer survival outcomes in breast cancer. Accordingly, the Commission on Cancer introduced a quality measure for receipt of therapeutic surgery within 60 days of diagnostic biopsy for stage I–III breast cancer patients in the non-neoadjuvant setting. It is unknown, however, what may contribute to mortality associated with treatment delay. Therefore, we investigated whether biopsy type moderates the effect of the mortality risk posed by treatment delay.MethodsRetrospective analysis of 31,306 women with stage I–III breast cancer diagnosed between 2003 and 2013 selected from the SEER-Medicare database was performed to determine whether needle biopsy type [core needle biopsy (CNB) or vacuum-assisted biopsy (VAB)] impacts time to treatment (TTT)-associated survival outcomes. Multivariable Fine-Gray competing risk survival models, adjusted for inverse propensity score weights, were used to determine the association between biopsy type, TTT, and breast cancer-specific mortality (BCSM).ResultsTTT ≥ 60 days was associated with 45% higher risk of BCSM (sHR = 1.45, 95% CI 1.24–1.69) compared to those with TTT < 60 days in stage I–III cases. Independent of TTT, CNB was associated with 28% higher risk of BCSM compared to VAB in stage II–III cases (sHR = 1.28, 95% CI 1.11–1.36), translating to a 2.7% and 4.0% absolute difference in BCSM at 5 and 10 years, respectively. However, in stage I cases, the BCSM risk was not associated with type of biopsy.ConclusionsOur results suggest that treatment delay ≥ 60 days is independently associated with poorer survival outcomes in breast cancer patients. In stage II–III, CNB is associated with higher BCSM than VAB. However, type of biopsy does not underlie TTT-associated breast cancer mortality risk.

Metabolic abnormalities and survival among patients with non-metastatic breast cancer

BackgroundResearch on the impact of metabolic abnormalities on breast cancer prognosis is limited by small samples and assessment of laboratory values at a single time point, often prior to cancer diagnosis and treatment. In this population-based cohort, time-updated laboratory values were adjusted for cancer treatment to assess the association between metabolic risk factors (glucose, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides) and breast cancer survival.Methods13,434 women diagnosed with stage I-III breast cancer from 2005-15 at Kaiser Permanente were included. All outpatient fasting glucose, HDL-C, LDL-C, and triglyceride values from diagnosis through 2019 or death were extracted from electronic medical records. Risk of breast cancer-specific mortality was evaluated with Cox proportional hazards models adjusted for metabolic labs, demographics, body mass index, diabetes, dyslipidemia and anti-hypertensive medications, tumor characteristics (stage, ER and HER2 receptor status) and cancer treatment (use of chemotherapy, tamoxifen, and aromatase inhibitors).ResultsMean (SD) age at diagnosis was 62.3 (11.8) years. Over a median follow-up of 8.6 years, 2,876 patients died; 1,080 of breast cancer. Patients with low HDL-C (≤ 45 vs. > 45 mg/dL) had higher breast cancer-specific mortality (HR, 1.77; 95% CI, 1.53-2.05), as did those with elevated fasting glucose (> 99 vs. 60-99 mg/dL) (HR, 1.19; 95% CI, 1.03-1.37). Elevated levels of triglycerides and LDL-C were not associated with breast cancer-specific mortality.ConclusionsHigh fasting glucose and low HDL-C evaluated over time after cancer diagnosis were associated with higher breast cancer mortality independent of cancer treatments and changes in other metabolic risk factors. Future studies should address whether pharmacologic or lifestyle treatment of glucose and lipids after breast cancer diagnosis can optimize survival outcomes.

Exploration of prognostic factors and the value of adjuvant chemotherapy in T1a,bN0M0 triple-negative breast cancer: a prospective cohort study based on the SEER database.

BackgroundThere are limited published studies on the prognostic predictors and the value of adjuvant chemotherapy (CT) in T1a,bN0M0 triple-negative breast cancer (TNBC) after local therapy. Therefore, the aim of the present study was to explore the prognostic predictors and the value of adjuvant CT in this population.MethodsWe identified T1a,bN0M0 TNBC cases registered in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. We analyzed associations between patient characteristics and overall survival (OS) and breast cancer-specific mortality (BCSM), and differences in OS and BCSM in a CT and no chemotherapy (no CT) cohort before and after propensity score matching.ResultsOf the 3,065 SEER patients, 1,534 (50.0%) received adjuvant CT. The median follow up was 57 months (interquartile range: 39–75 months). The 5-year OS and cumulative BCSM were 93.6% and 3.3%, respectively. Younger age was not associated with lower OS or higher BCSM in the total and no CT cohorts. Higher histologic grade was associated with lower OS in the no CT cohort, and T1b tumors were associated with higher BCSM in the total cohort. Multivariable analysis showed no association between adjuvant CT and OS or BCSM.ConclusionsPatients with T1a,bN0M0 TNBC had an excellent prognosis with or without adjuvant CT. For this population, higher histologic grade and larger tumor size were predictors of poor prognosis, although the effect of age was complex. Our data did not support using adjuvant CT in patients with T1a,bN0M0 TNBC.

Association of metabolic risk factors with breast cancer survival in a population-based cohort.

12089 Background: Metabolic abnormalities may impact breast cancer prognosis, but research has been limited by small samples and assessment of laboratory values at a single time point, often prior to cancer diagnosis and treatment. In a population based cohort, we utilized time-updated laboratory values and adjusted for cancer treatment to assess the association between metabolic risk factors (glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides) and breast cancer survival. Methods: 13,434 women diagnosed with stage I-III breast cancer from 2005-15 at Kaiser Permanente were included. All outpatient fasting glucose, HDL, LDL, and triglyceride values from diagnosis through 2019 or death were extracted from electronic medical records. Lab values were updated a median of 5 times between 1-7 years post-diagnosis. Risk of breast cancer-specific mortality was evaluated with Cox proportional hazards models adjusted for metabolic labs, demographics, body mass index, and diabetes, and then for dyslipidemia and anti-hypertensive medications, tumor characteristics (stage, ER and HER2 receptor status) and cancer treatment (use of chemotherapy, and tamoxifen v. aromatase inhibitors). Results: Mean (SD) age at diagnosis was 62.3 (11.8) years. Over median follow-up of 9 years, 2,876 patients died (1,080 of breast cancer). Patients with low HDL (≤45 vs. &gt;45 mg/dL) had higher breast cancer-specific mortality (HR, 1.87; 95% CI, 1.62-2.16); high levels of glucose, triglycerides, and LDL were not associated. The increased risk associated with low HDL persisted after adjusting for tumor characteristics, cancer treatment, and medications. Conclusions: Low HDL evaluated over time after cancer diagnosis is associated with higher breast cancer mortality independent of cancer treatments and changes in other metabolic risk factors. Cholesterol may play a role in breast cancer due to its role in cell membrane structure, signaling pathways, and steroid hormone synthesis. Future studies should address whether pharmacologic or lifestyle treatment of lipids after breast cancer diagnosis can optimize survival outcomes.[Table: see text]

Cardiometabolic risk factors, physical activity, and postmenopausal breast cancer mortality: results from the Women\u2019s Health Initiative

BackgroundHigher physical activity levels are associated with lower breast cancer-specific mortality. In addition, the metabolic syndrome is associated with higher breast cancer-specific mortality. Whether the physical activity association with breast cancer mortality is modified by number of metabolic syndrome components (cardiometabolic risk factors) in postmenopausal women with early-stage breast cancer remains unknown.MethodsCardiovascular risk factors included high waist circumference, hypertension, high cholesterol, and diabetes. Breast cancers were verified by medical record review. Mortality finding were enhanced by serial National Death Index queries. Cox proportional hazards regression models were used to estimate associations between baseline physical activity and subsequent breast cancer-specific and overall mortality following breast cancer diagnosis in Women’s Health Initiative participants. These associations were examined after stratifying by cardiometabolic risk factor group.ResultsAmong 161,308 Women’s Health Initiative (WHI) participants, 8543 breast cancers occurred after 9.5 years (median) follow-up in women, additionally with information on cardiometabolic risk factors and physical activity at entry. In multi-variable analyses, as measured from cancer diagnosis, higher physical activity levels were associated with lower all-cause mortality risk (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.78–0.95, trend P < 0.001) but not with breast cancer-specific mortality (HR 0.85, 95% CI 0.70 to 1.04, trend P = 0.09). The physical activity and all-cause mortality association was not significantly modified by cardiometabolic risk factor number.ConclusionsAmong women with early-stage breast cancer, although higher antecedent physical activity was associated with lower risk of all-cause mortality, the association did not differ by cardiometabolic risk factor number.

Abstract 789: Benign breast disease and all-cause and breast cancer-specific mortality among postmenopausal women in the Women's Health Initiative

Abstract INTRODUCTION: Benign breast disease (BBD) describes a heterogeneous group of premalignant lesions associated with an increased risk of breast cancer development, especially in those with proliferative BBD with atypia. Whether BBD is associated with higher all-cause mortality is unsettled. Therefore, we examined the association between incident BBD, BBD histotypes and all-cause and breast cancer-specific mortality among WHI participants. METHODS: Included were 68,132 postmenopausal women enrolled in the WHI clinical trials from 1993-1998 at 40 US clinical centres, followed up through March 2019. In these trials, serial mammography was mandated and compliance was high. Cases were participants in the BBD ancillary study (AS)130 with incident BBD confirmed by central pathology review. The comparison group included all other clinical trial participants (intervention and control groups). Cox proportional hazard regression models, stratified by baseline age, clinical trial arms and WHI extension study participation, were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause and breast cancer-specific mortality in association with BBD. Analyses were adjusted for age, race/ethnicity, education, income, smoking, BMI, waist circumference, energy intake, alcohol, physical activity, reproductive factors, family history of breast cancer, Gail model score, history of menopausal hormone therapy (MHT) use and history of comorbidities. RESULTS: Compared to women without incident BBD (n=43,439), women with incident BBD (n=3,467) were younger (p&amp;lt;0.001), more likely to have a higher education level (p=0.003), higher income (p&amp;lt;0.001), lower BMI (p=0.003) and waist circumference (p=0.002), a Gail risk score of &amp;gt;1.75 (p&amp;lt;0.001), a family history of breast cancer (p&amp;lt;0.001) and used MHT (p&amp;lt;0.001). There were 737 deaths among the BBD case group and 8,949 deaths among the non-case group. In adjusted analyses, no association was observed between incident BBD and all-cause mortality (HR:0.92, 95%CI: 0.83, 1.01). In adjusted analyses stratified by BBD, compared to women without BBD, no association for all-cause mortality was observed for women with non-proliferative BBD (n=374; HR:0.96; 95%CI: 0.84, 1.09), proliferative BBD without atypia (n=309; HR:0.91, 95%CI: 0.79, 1.05) or proliferative BBD with atypia (n=54; HR:0.72, 95% CI: 0.51, 1.03). In secondary analyses, compared to women without incident BBD, women with incident BBD had a statistically significantly higher breast cancer-specific mortality both for BBD overall and for each BBD histotype. CONCLUSIONS: In postmenopausal women, while a BBD diagnosis was associated with a statistically significant higher risk of breast cancer-specific mortality, irrespective of histotype, a BBD diagnosis was not associated with higher all-cause mortality. Citation Format: Maeve Mullooly, Kathy Pan, Sowmya Vasan, Gretchen L. Gierach, Dorothy S. Lane, Aladdin H. Shadyab, Juhua Luo, Lihong Qi, Kathleen E. Bennett, Thomas E. Rohan, Rowan Chlebowski. Benign breast disease and all-cause and breast cancer-specific mortality among postmenopausal women in the Women's Health Initiative [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 789.

Prior DCIS and overall mortality in women with stage I breast cancer.

e12593 Background: Whether a prior diagnosis of ductal carcinoma in situ (DCIS) impacts women later diagnosed with invasive breast cancer is unclear. If localized breast cancer following DCIS is more aggressive than localized breast cancer alone, this could inform therapy decisions. To our knowledge, no study has examined the impact of prior DCIS on overall mortality in women with stage I invasive breast cancer. The study objective was to determine if overall mortality for women with stage I breast cancer with prior DCIS is different from those with stage I disease without prior DCIS. Our hypothesis was that women with prior DCIS would have higher mortality compared to those without prior DCIS. Methods: 302,484 patients with stage I cancer diagnosed from 1998 to 2016 were ascertained from SEER. Of these, 5,011 (1.7%) had prior DCIS. Patients with DCIS were matched 1:2 to women with no prior DCIS based on age, year of diagnosis, race/ethnicity, marital status, and invasive breast cancer characteristics including histology, tumor grade, tumor size, T stage, N stage, ER/PR status, surgery type, radiation, and chemotherapy status. The primary study outcome was overall mortality. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Results: Cases and controls had similar demographics. Compared to women with stage I breast cancer without prior DCIS, overall mortality was statistically significantly lower in women with stage I breast cancer with prior DCIS (hazard ratio [HR] 0.89 95% confidence interval [CI]0.80-0.98). Other factors associated with overall mortality were bilateral mastectomy (adjusted HR: 0.62; 95% CI: 0.49-0.78), radiation therapy (adjusted HR: 0.64; 95% CI: 0.56-0.75) and chemotherapy (adjusted HR: 0.85; 95% CI: 0.72-0.99). Factors associated with higher overall mortality included age (trend p &lt; 0.001), tumor grade (trend p = 0.003), and negative PR receptor status (adjusted HR: 1.29; 95% CI: 1.13-1.45). Breast cancer specific mortality, however, was statistically significantly higher in women with prior DCIS to their breast cancer diagnosis compared to women without prior DCIS to their breast cancer diagnosis (HR 1.24 95% CI 1.01-1.52). Conclusions: Contrary to our hypothesis, women with prior DCIS and subsequent stage I breast cancer have lower overall mortality compared to matched controls with stage I breast cancer without prior DCIS. In contrast, those with prior DCIS have higher breast cancer specific mortality than those without prior DCIS. Reasons for this discrepancy are unknown, but since DCIS is most commonly diagnosed on mammogram, differences may be related to sociodemographic characteristics that are associated with both higher screening adherence and higher overall survival, such as higher income, higher education achievement , and higher access to health care.

Consumption of sugar-sweetened and artificially sweetened beverages and breast cancer survival.

The activation of insulin pathways is hypothesized to promote tumor growth and worsen breast cancer survival. Sugar-sweetened beverages (SSBs) can lead to a higher risk of insulin resistance and may affect survival. The authors prospectively evaluated the relation of postdiagnostic SSB and artificially sweetened beverage (ASB) consumption with mortality among women with breast cancer. In total, 8863 women with stage I through III breast cancer were identified during follow-up of the Nurses' Health Study (NHS; 1980-2010) and Nurses' Health Study II (NHSII; 1991-2011). Women completed a validated food frequency questionnaire every 4 years after diagnosis and were followed until death or the end of follow-up (2014 for the NHS and 2015 for the NHSII). Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of breast cancer-specific and all-cause mortality after adjusting for measures of adiposity and other potential predictors of cancer survival. With a median follow-up of 11.5 years, 2482 deaths were prospectively documented, including 1050 deaths from breast cancer. Compared with women who had no consumption, women who had SSB consumption after diagnosis had higher breast cancer-specific mortality (>1 to 3 servings per week: HR, 1.31 [95% CI, 1.09-1.58]; >3 servings per week: HR, 1.35 [95% CI, 1.12-1.62]; Ptrend = .001) and all-cause mortality (>1 to 3 servings per week: HR, 1.21 [95% CI, 1.07-1.37]; >3 servings per week: HR, 1.28 [95% CI, 1.13-1.45]; Ptrend = .0001). In contrast, ASB consumption was not associated with higher breast cancer-specific or all-cause mortality. Furthermore, replacing 1 serving per day of SSB consumption with 1 serving per day of ASB consumption was not associated with a lower risk of mortality. Higher postdiagnostic SSB consumption among breast cancer survivors was associated with higher breast cancer-specific mortality and death from all causes.

Management of Cancer Patients during Coronavirus Disease 2019 Pandemic: A Literature Review

Introduction: The number of confirmed cases of Coronavirus Disease 2019 (COVID-19) in the world has been increasing significantly since December 2019. Cancer patients are one of the vulnerable populations to become severe cases of COVID-19 or death when they are contacted with COVID-19. A treatment delay is associated with higher breast cancer-specific mortality and all-cause mortality. However, there is still limited data about how to manage cancer patients in this pandemic of COVID-19. This study aims to appraise the current evidence about the management of cancer patients during the COVID-19 pandemic.Method: We searched and found 16 articles evaluating the management of cancer patients during the COVID-19 pandemic by searching in PubMed and EMBASE databases. We only included articles discussing COVID-19 and cancer in adults. There were three observational trials, four review articles, two case reports, six letters to the editor, and one guideline.Results: There were several recommendations regarding patient care in the COVID-19 era. Firstly, outpatient visits, such as follow-up and surveillance of cancer patients, should be postponed. Alternatively, they can do teleconsultation, and their drugs will be delivered to their homes. Stratification and screening for the risk of COVID-19 infection should be done to those who needed urgent or emergency surgery. Otherwise, elective surgery should be postponed. However, several cases can be proceeded after discussion in the Multidisciplinary Team (MDT). Adjuvant and palliative chemotherapy should also be done as scheduled after discussing in MDT. Patients with ongoing radiation treatment should be continued as daily scheduled. Meanwhile, new patients should be carefully evaluated, and those with stable cancer can be postponed for treatment Conclusions: There is still scarce evidence related to the management of cancer patients during the COVID-19 pandemic. Further studies, in terms of stratification, risk, and management of cancer patients during the pandemic, need to be done to get better evidence on it.

Ductal Carcinoma In Situ of the Breast: Perspectives on Tumor Subtype and Treatment.

Objective To evaluate ductal carcinoma in situ (DCIS) characteristics and the effect of different treatment strategies. Patients and Methods. Using data with known hormone receptor (HoR) and human epidermal growth factor receptor 2 (HER2) status obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2014, the study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS), and breast cancer-specific mortality (BCSM). Results A total of 3415 patients with DCIS were eligible. Compared with HoR+/HER- subgroup, patients with triple-negative (TN) and HoR-/HER+ were commonly higher in grade, larger in size, and tended to receive mastectomy (P < 0.05). The multivariate analysis revealed that patients with TN were more likely to have a poorer OS and show a higher breast cancer-specific mortality compared with the HoR+/HER- subgroup (P < 0.05). Multivariate analysis on the history of local treatment and surgery showed patients receiving breast-conserving surgery (BCS) plus radiotherapy (R) and BCS plus axillary lymph node dissection was likely to improve OS without affecting breast cancer-specific mortality (P < 0.05). Conclusion The results demonstrate that DCIS associated with TN subtype portends poor prognosis. Meanwhile, BCS plus R was a preferable option and resulted in survival rates better than those achieved with mastectomy, and SLNB should be considered as an appropriate assessment of axillary staging in patients with DCIS.

Pre- and post-diagnostic intake of whole grain and dairy products and breast cancer prognosis: the Danish Diet, Cancer and Health cohort

Fiber rich foods and dairy products have been suggested to be associated with breast cancer prognosis, though existing research is limited and either report on pre- or post-diagnostic dietary intake in relation to breast cancer prognosis. We investigated the associations between intake of whole grain (WG) and dairy products assessed both pre- and post-diagnostically in relation to breast cancer prognosis. A total of 1965 women from the Diet, Cancer and Health cohort who were diagnosed with breast cancer between baseline (1993-1997) and December 2013 were included and followed for a median of 7years after diagnosis. During follow-up, 309 women experienced breast cancer recurrence and 460 women died, of whom 301 died from breast cancer. Dietary assessment by food frequency questionnaires was obtained up to three times, pre- and post-diagnostic, over a period of 18years. Cox proportional hazard models were used to estimate hazard ratios. No associations were observed between pre- or post-diagnostic intake of total WG or total dairy products and breast cancer prognosis. A high pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality (HR 0.76, 95% CI 0.59-0.99), whereas high post-diagnostic intake of rye bread was associated with higher breast cancer-specific mortality (HR 1.29, 95% CI 1.02-1.63). A generally high intake of cheese was associated with a higher recurrence rate. Pre-diagnostic intake of oatmeal/muesli was associated with lower all-cause mortality,and post-diagnostic intake of rye bread was associatedwith higher breast cancer specific mortality.

Particulate Matter and Traffic-Related Exposures in Relation to Breast Cancer Survival.

Although particulate matter (PM) has not been consistently associated with breast cancer risk, two studies have reported harmful associations for breast cancer survival. We examined PM exposures and breast cancer survival in two U.S.-based prospective cohort studies. The Nurses' Health Study (NHS) and NHSII are cohorts with detailed data on medical history, lifestyle factors, and causes of death. Women with Stage I-III breast cancer (n = 8,936) were followed through June 2014. Residential PM was estimated using spatio-temporal models. We performed Cox regression to estimate hazard ratios (HR) of breast cancer-specific mortality and all-cause mortality for 10 μg/m3 increases in post-diagnosis PM. There were 1,211 breast cancer-specific deaths. Overall, PM was not associated with breast cancer-specific mortality [PM2.5: HR, 1.09; 95% confidence interval (CI), 0.87-1.36; PM2.5-10: HR, 1.03; 95% CI, 0.85-1.24; PM10: HR, 1.05; 95% CI, 0.89-1.24], but was associated with modest increases in all-cause mortality (PM2.5: HR, 1.12; 95% CI, 0.96-1.30; PM2.5-10: HR, 1.12; 95% CI, 1.00-1.24; PM10: HR, 1.09; 95% CI, 1.01-1.18). However, among participants with Stage I disease, PM2.5 was associated with higher breast cancer-specific mortality (HR, 1.64; 95% CI, 1.11-2.43). PM was not associated with breast cancer-specific death overall; however, higher PM was associated with all-cause mortality. Higher PM2.5 was associated with higher breast cancer-specific mortality among patients with Stage I breast cancer even after adjustment. Studies on ambient PM and breast cancer survival demonstrate that PM2.5 may have broader health effects than previously recognized and warrants further research on breast tumor progression.

The insulin-like growth factor family and breast cancer prognosis: A prospective cohort study among postmenopausal women in Denmark

ObjectiveCirculating levels of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have been associated with breast cancer (BC) risk. The evidence in relation to BC prognosis is limited. We aimed to evaluate the association between pre-diagnostic serum levels of IGF-I, IGF-II, IGFBP-2, IGFBP-3 and BC prognosis (i.e. recurrence, BC specific mortality and all-cause mortality) among women diagnosed with BC. We hypothesized that higher serum levels of IGFs and IGFBPs were associated with poor BC prognosis and that the associations were modified by estrogen receptor (ER) status. DesignFrom the Danish Diet, Cancer and Health cohort, 412 postmenopausal women diagnosed with incident BC within 5 years of cohort baseline (1993–1997) were identified. Baseline serum samples were analyzed for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Follow-up was carried out through 2014 by linkage to national Danish registries. Exposures were related to BC prognosis by Cox Proportional Hazard models; effect modification by ER status was investigated and sensitivity analyses by follow-up time were made. ResultsDuring a median of 15 years, 106 women experienced recurrence and 172 died (118 due to BC). Overall, no associations were observed between IGF-I, IGF-II, IGFBP-2, IGFBP-3 and BC prognosis and no effect modification by ER status was observed. However, higher levels of IGF-II were associated with higher BC specific mortality [Hazard Ratio (HR) (95% Confidence Intervals (CI)): 1.43 (1.01–2.04)] within 10 years of follow-up. Likewise, higher levels of IGFBP-2 were associated with higher BC specific mortality [HR (95% CI): 1.87 (1.19–2.94)] within 5 years of follow-up. In contrast, higher levels of IGFBP-3 were associated with lower risk of recurrence [HR (95% CI): 0.76 (0.60–0.97)] at 5 years of follow-up and BC specific mortality [HR (95% CI): 0.80 (0.65–0.98)] within 10 years of follow-up. ConclusionsThe present study did not support an association between higher serum levels of IGFs, IGFBPs and adverse BC prognosis. However, it is possible that the role of the IGF family in the etiology of the 5–10 year BC prognosis is different from that of longer-term BC prognosis.

Selective serotonin reuptake inhibitor use and breast cancer survival: a population-based cohort study

BackgroundNearly 50% of breast cancer patients suffer from depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for depression, have been implicated in breast cancer development through increased prolactin levels and tamoxifen metabolism inhibition. Previous studies of breast cancer progression have focused on tamoxifen users, or have been limited by their small sample size and methodology. Therefore, we used UK population-based data to more robustly investigate the association between SSRI use and cancer-specific mortality.MethodsA cohort of patients with newly-diagnosed breast cancer between 1998 and 2012 was selected from English cancer registries and linked to prescription records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used Cox regression models to calculate hazard ratios (HRs) comparing mortality between post-diagnostic SSRI users and non-users (using time-dependant covariates), after adjusting for demographics, comorbidities and pre-diagnosis use of hormone replacement therapy or oral contraceptives. We conducted several additional analyses to assess causality.ResultsOur cohort included 23,669 breast cancer patients, of which 2672 used SSRIs and 3053 died due to their breast cancer during follow-up. After adjustment, SSRI users had higher breast cancer-specific mortality than non-users (HR = 1.27; 95% confidence interval (CI) 1.16, 1.40). However, this association was attenuated when restricting to patients with a prior history of depression (HR = 1.14; 95% CI 0.98, 1.33), and when comparing to users of other antidepressant medications (HR = 1.06; 95% CI 0.93, 1.20). There was some evidence of higher mortality among long-term SSRI users, even when restricting to patients with prior depression (HR = 1.54; 95% CI 1.03, 2.29).ConclusionsIn this large breast cancer cohort, SSRI use was associated with a 27% increase in breast cancer mortality. The cause of this is unknown; however, confounding by indication seems likely as it was largely attenuated when restricting to patients with prior depression, or when comparing SSRIs to other antidepressant medications. Clinicians should not be unduly concerned when prescribing SSRIs to breast cancer patients, but the increase in mortality among long-term SSRI users warrants further investigation.

Breast cancer in male veterans: The Veterans Affairs (VA) informatics and computing infrastructure (VINCI) big data analysis.

1559 Background: Male breast cancer (MBC) management from diagnosis to treatment is generalized from female breast cancer (FBC) because of its rarity and paucity in literature. VINCI is a unique database for cross sectional and longitudinal analysis. The objective of this retrospective analysis was to compare characteristics and outcome of MBC with FBC in veterans. Methods: Detailed demographics, diagnosis, treatment and outcome of all patients diagnosed with breast cancer between 1998 and 2016 at 152 VA medical centers were obtained and analyzed with Chi-square and t-test univariate statistics. Results: In total 9765 patients' records were reviewed, 1613 MBC were compared with 8152 FBC. The mean age at diagnosis is 68.5 and 57.3 years for MBC and FBC, respectively (Table1). After a median follow up of 3.5 years, 48% MBC and 22% FBC died. Breast cancer mortality is 18% and 9% in MBC and FBC, respectively. A cox regression survival analysis indicates that males were 33% (Hazard Ratio 1.33, P=&lt;0.0001) more likely to die from breast cancer than females. Conclusions: This is the largest comparison series of MBC with FBC to date in the Veteran population to author’s knowledge. Males have higher breast cancer specific mortality than females most likely because of older age and higher stage at the time of diagnosis. Differences in the biology and pathology may be contributing factors which needs further prospective studies. [Table: see text]

Abstract PR05: Ancestry as a potential modifier of gene expression in luminal B tumors among Colombian women

Abstract Background: Differences in outcome of breast cancer according to race/ethnicity have been reported. African American women have higher breast cancer-specific mortality rates compared to non-Hispanic White women (NHW). Although these differences have been attributed to the high prevalence of basal-like subtype among African Americans, these women have also less favorable outcome in less aggressive tumors when compared to NHW. Hispanic/Latino (H/L) populations are a genetically admixed and heterogeneous group, with variable levels of European, Native American and African ancestries. Some studies suggest that breast cancer-specific mortality is higher in U.S. Latinas compared to NHW even after adjustment for socioeconomic status and education. The molecular profile of breast cancer has been widely described in NHWs but knowledge is lacking in Latinas. We have previously reported that the most prevalent breast cancer intrinsic subtype in Colombian women was Luminal B. In this study we explored ancestry-associated differences in molecular profiles of luminal B tumors among these highly admixed women. Methods: To identify ancestry-associated differentially expressed genes in Luminal B tumors, we performed a whole-transcriptome RNA-seq analysis in 42 luminal tumors (21 Luminal A and 21 Luminal B) from Colombian women. Genetic ancestry was estimated from a panel of 80 ancestry-informative markers (AIM). We categorized patients according to luminal subtype and to the proportion of European ancestry (Low European ancestry group: ancestry proportion below the median; High European ancestry: ancestry proportion above the median).. We compared luminal B against luminal A tumors according to the assigned ancestry groups. We used DESeq2 package form R to test differential gene expression between the two tumor subtypes and by ancestry category. Genes with adjusted pvalue less than 0.05 were considered statistical significant. Results: We found 30 differentially expressed genes (pvalue &amp;lt; 0.05) by genetic ancestry among Luminal B tumors from which 27 were differentially expressed in the less European luminal B tumors and 3 in the more European group. Tests of interaction suggest that ancestry is a statistically significant modifier of expression for the following genes for Low European Ancestry group: CENPF, SNORA54, AIF1L, TNFSF13, LRRC1, ARHGAP33, ONECUT2, CDK12, BUB1, NTRK2, HES1); and FDXACB1, RAB26, ATP8B3 for the High European Ancestry group. An exploratory analysis of these genes reveals enrichment of pathways associated to ERBB signaling in the Low European Ancestry group. Conclusions: Our results suggest that the proportion of European genetic ancestry in Colombian women might modify gene expression in luminal B tumors. Further analysis will be needed to confirm these findings. Citation Format: Silvia J. Serrano-Gomez, Carolina Sanabria, Melody C. Baddoo, Nataly Cruz-Rodriguez, Jone Garai, Gustavo Hernandez-Suarez, Juan Carlos Mejia, Lucio Miele, Chindo Hicks, Laura Fejerman, Jovanny Zabaleta. Ancestry as a potential modifier of gene expression in luminal B tumors among Colombian women. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr PR05.

Poorer breast cancer survival outcomes in males than females might be attributable to tumor subtype

Background & AimsSubstantial controversy exists regarding the differences in tumor subtypes between male breast cancer (MBC) and female breast cancer (FBC). This is the largest population-based study to compare MBC and FBC patients.MethodsUsing data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2012, a retrospective, population-based cohort study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS) and breast cancer-specific mortality (BCSM) between males and females.ResultsIn all, 181,814 BC patients (1,516 male and 180,298 female) were eligible for this study. The male patients were more likely to be black, older, and have lower histological grades, more advanced stages, larger tumors, more lymph node and distant metastases and human epidermal growth factor receptor 2 (HER2)-negative tumors (each p<0.05). A matched analysis showed that the 2-year OS was 91.2% and 93.7% and that the BCSM was 2.2% and 2.5% for male and female patients, respectively. The univariate analysis showed that male triple-negative (TN), hormone receptor (HoR)-positive/HER2-positive and HoR-positive/HER2-negative patients had poorer OS (p <0.01). Meanwhile, the HoR-positive/HER2-positive and TN subtypes were associated with a higher BCSM in MBC patients (p<0.01). The multivariate analysis revealed that TN MBC patients had poorer OS and BCSM (p<0.05). Simultaneously, the results showed that male patients in the HoR-positive/HER2-negative subgroup were less likely to die of BC when adjusting for other factors (p<0.05).ConclusionsThe analysis of 2-year OS and BCSM among the BC subtypes showed clear differences between MBC and FBC patients with the TN subtype; these differences warrant further investigation

Strategies for the Management of Early-Stage Breast Cancer in Older Women.

Older patients with breast cancer (aged ≥65 years) are often undertreated with both locoregional and systemic therapies and have been shown to have higher breast cancer-specific mortality. These patients are also excluded from most clinical trials; therefore, treatment recommendations are extrapolated from younger populations. The data that do exist, however, show that older patients usually tolerate and respond well to conventional treatments. When selecting treatments for breast cancer, age should not be the chief consideration; comorbidities and functional status are also important, as is life expectancy. For patients with an estimated survival of less than 5 years, aggressive treatment may be discouraged; however, if the estimated survival is 5 years or more, treatment according to recurrence risk is recommended. In the curative setting, undertreatment should be avoided.

Lifestyle influences on the association between pre-diagnostic hormone replacement therapy and breast cancer prognosis—Results from The Danish ‘Diet, Cancer and Health’ prospective cohort

ObjectivesThe association between pre-diagnostic hormone replacement therapy (HRT) and breast cancer specific mortality as well as potential influences from other lifestyle factors on the association was investigated. Study designFemale participants from the prospective cohort “Diet, Cancer, and Health” diagnosed with breast cancer (BC) were identified and their pre-diagnostic HRT use evaluated for association with tumour biology and breast cancer outcome in multivariate analysis. Main outcome measureBreast cancer specific mortality. ResultsOf the 1212 patients originally considered 1064 were included. Of these, 105 women died from breast cancer during a median follow-up of 6.3 years (range 0.2–14.3 years). In multivariate analyses women who used HRT at enrolment into the cohort study had 47% lower risk of dying from breast cancer as compared to women who had previously or never used HRT (adjusted HR: 0.53; 95% CI, 0.37–0.85). Pre-diagnostic HRT use was associated with smaller tumour size at the time of diagnosis and a higher frequency of receptor positive breast cancer. Paradoxically, a high pre-diagnostic intake of vitamin D supplements was associated with HRT use but also with a higher BC specific mortality (HR: 1.47; 95% CI, 1.07–2.00) ConclusionsHRT use at enrolment was associated with breast tumours of smaller size at the time of diagnosis and positive receptor status, and with a lower BC mortality. The found association between vitamin D from supplements and higher BC mortality warrants further exploration.

Screening mammography rates in women with diabetes.

25 Background: Women with diabetes are at an increased risk of developing breast cancer, present with later stage disease, and experience higher breast cancer-specific mortality compared to nondiabetic women. Thus, it is imperative that diabetic women undergo routine screening mammography. Previous studies have shown conflicting results with smaller studies showing lower screening mammography rates among diabetics while a study using national self-report data showed that diabetic women were equally likely to be screened compared to nondiabetic women. Given the conflicting data and limitations of previous studies, we aimed to study receipt of mammography in diabetic women using a nationally representative administrative claims database. Methods: This was a retrospective study using a nationally representative administrative claims database from January 1, 2010, through December 31, 2012. We compared rates of receipt of mammography within a 2-year time frame in diabetic and nondiabetic women ages 40 to 64. We used Healthcare Effectiveness Data and Information Set (HEDIS) logic to define women with diabetes. We used CPT and ICD-9 codes to identify mammogram services received. We calculated odds ratios with 95% confidence intervals to compare mammogram rates among diabetics compared to nondiabetics. Results: 1,723,674 nondiabetic women and 133,973 diabetic women were identified. Among women ages 40 to 49, diabetic women had significantly decreased mammography rates compared to nondiabetic women (OR 0.84; 95% CI 0.83, 0.85). Rates were also lower in diabetic women ages 50 to 64 (OR 0.88; 95% CI 0.88, 0.91). Despite lower mammography rates among diabetics, diabetic women had 1.78 times more visits than nondiabetic women. Conclusions: Women with diabetes are less likely to undergo routine screening mammography than women without diabetes, despite having more encounters with health care providers. This study serves as a reminder to provide timely preventive health services to all patients regardless of medical comorbidities.