Reduction In Breast Cancer-specific Mortality Research Articles

The Benefits of Physical Activity to Reduce Mortality in Postmenopausal Breast Cancer Patients: A Literature Review

Background: Breast cancer cases are more commonly diagnosed in postmenopausal women and the risk increases with age. Along with an increased vulnerability to breast cancer, increasing age also carries a higher risk of other health problems. Postmenopausal breast cancer patients frequently have one or more pre-existing comorbid conditions at the time of diagnosis. Higher physical activity can reduce breast cancer-specific and overall mortality. However, the vast majority of early breast cancer survivors experience a decrease in physical activity. This study aimed to determine the relationship between physical activity and the reduction of Breast Cancer-Specific Mortality (BCSM) and overall mortality in postmenopausal breast cancer survivors.Methods: This research uses a literature review design by conducting a journal search through Google Scholar, PubMed, and ScienceDirect. The keywords used are (“Physical activity” or Exercise) and (“Breast Cancer” or “Breast Neoplasm”) and (Mortality) and (“Post-menopause”).Results: Seven studies were included in this review. A total of 6276 deaths were reported. Only 3 out of 6 studies reported that there is a significant benefit between physical activity and reduction in breast cancer-specific mortality. Contrarily, all studies reported that there is a significant benefit between physical activity and overall mortality reduction, but at a certain intensity level. Conclusions: Our data suggest that physical activity, whether pre-diagnosis or post-diagnosis, is associated with a better prognosis of breast cancer in postmenopausal women.

The effect of the Flemish breast cancer screening program on breast cancer-specific mortality: A case-referent study

BackgroundBreast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality. MethodsWe performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses. ResultsWe identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44–0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant. ConclusionOur results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment.

Healthy Eating and Mortality among Breast Cancer Survivors: A Systematic Review and Meta-Analysis of Cohort Studies.

This systematic review examined the effect of diet quality, defined as adherence to healthy dietary recommendations, on all-cause and breast cancer-specific mortality. Web of Science, Medline, CINAHL, and PsycINFO databases were searched to identify eligible studies published by May 2021. We used a random-effects model meta-analysis in two different approaches to estimate pooled hazard ratio (HR) and 95% confidence interval (CI) for highest and lowest categories of diet quality: (1) each dietary quality index as the unit of analysis and (2) cohort as the unit of analysis. Heterogeneity was examined using Cochran’s Q test and inconsistency I2 statistics. The risk of bias was assessed by the Newcastle–Ottawa Scale for cohort studies, and the quality of evidence was investigated by the GRADE tool. The analysis included 11 publications from eight cohorts, including data from 27,346 survivors and seven dietary indices. Both approaches yielded a similar effect size, but cohort-based analysis had a wider CI. Pre-diagnosis diet quality was not associated with both outcomes. However, better post-diagnosis diet quality significantly reduced all-cause mortality by 21% (HR = 0.79, 95% CI = 0.70, 0.89, I2 = 16.83%, n = 7) and marginally reduced breast cancer-specific mortality by 15% (HR = 0.85, 95% CI = 0.62, 1.18, I2 = 57.4%, n = 7). Subgroup analysis showed that adhering to the Diet Approaches to Stop Hypertension and Chinese Food Pagoda guidelines could reduce breast cancer-specific mortality. Such reduction could be larger for older people, physically fit individuals, and women with estrogen receptor-positive, progesterone receptor-negative, or human epidermal growth factor receptor 2-positive tumors. The risk of bias in the selected studies was low, and the quality of evidence for the identified associations was low or very low due to imprecision of effect estimation, inconsistent results, and publication bias. More research is needed to precisely estimate the effect of diet quality on mortality. Healthcare providers can encourage breast cancer survivors to comply with healthy dietary recommendations to improve overall health. (Funding: University of Central Florida Office of Undergraduate Research, Registration: PROSPERO-CRD42021260135).

Carvedilol blocks neural regulation of breast cancer progression in vivo and is associated with reduced breast cancer mortality in patients

PurposeThe sympathetic nervous system drives breast cancer progression through β-adrenergic receptor signalling. This discovery has led to the consideration of cardiac β-blocker drugs as novel strategies for anticancer therapies. Carvedilol is a β-blocker used in the management of cardiovascular disorders, anxiety, migraine and chemotherapy-induced cardiotoxicity. However, little is known about how carvedilol affects cancer-related outcomes. MethodsTo address this, we investigated the effects of carvedilol on breast cancer cell lines, in mouse models of breast cancer and in a large cohort of patients with breast cancer (n = 4014). ResultsTreatment with carvedilol blocked the effects of sympathetic nervous system activation, reducing primary tumour growth and metastasis in a mouse model of breast cancer and preventing invasion by breast cancer cell lines. A retrospective analysis found that women using carvedilol at breast cancer diagnosis (n = 136) had reduced breast cancer-specific mortality compared with women who did not (n = 3878) (5-year cumulative incidence of breast cancer deaths: 3.1% versus 5.7%; p = 0.024 and 0.076 from univariate and multivariable analyses, respectively) after a median follow-up of 5.5 years. ConclusionsThese findings provide a rationale to further explore the use of the β-blocker carvedilol as a novel strategy to slow cancer progression.

Abstract C052: Premenopausal oophorectomy and survival among women with breast cancer: Evidence of effect measure modification by family history status

Abstract In the US, bilateral oophorectomies are frequently performed before menopause for one of two reasons: 1) in concert with hysterectomy for benign gynecologic conditions or 2) prevention of breast or ovarian cancer risk and mortality. Prior literature has consistently shown a reduction in breast cancer-specific mortality among women who had premenopausal hysterectomy with bilateral oophorectomy (H +BO) prior to their breast cancer diagnosis. The present study sought to assess whether the relationship between prediagnosis premenopausal H + BO and breast cancer-specific mortality differed by family history status in women with breast cancer. It is hypothesized that women who may have prognostically different breast cancer due to having family history disproportionately benefit from premenopausal H+ BO compared to more average-risk women with no family history. This study analyzed data from Phases 1 and 2 of the Carolina Breast Cancer Study (CBCS), a population-based study of Black and White women prospectively identified in central and eastern North Carolina with newly diagnosed breast cancer between 1993 and 2001. Women with invasive breast cancer with known gynecologic surgical status were included (n=1,723). Gynecologic surgery was defined as: no surgery; hysterectomy with bilateral oophorectomy (H+BO); hysterectomy with conservation of ≥1 ovary (H + OC). Cause-specific mortality was ascertained using the National Death Index, last updated in 2016. Hazard ratios (HR) and 95% confidence intervals (CI) for breast cancer-specific mortality were estimated with Cox proportional hazard models. Models were then stratified by family history status, the self-reporting of one or more first-degree relatives with a family history of breast cancer. Models were adjusted for race, age at diagnosis, smoking, alcohol use, menopausal hormone therapy use and reproductive history factors. All participants still living at the end of follow-up were right censored. Among 1,723 women in the sample, 44% (n=759) were Black and 56% (n=964) were White. There were 836 deaths, of which 447 were from breast cancer. In this population, 74.1% (n=1,276) of women reported having no previous premenopausal gynecologic surgery, 8.8% (n=152) reported having H + BO and 17.1% (n=295) reported H + OC. Compared to women who had not had premenopausal gynecologic surgery, the overall adjusted HR for breast cancer-specific mortality associated with H+BO was 0.68 (95% CI: 0.49,0.96) and 0.90 (95% CI: 0.72,1.12) for women with H+OC. In models stratified on family history, the HR for women with H+BO was 0.11 (95% CI: 0.03,0.42) for those with family history and 0.90 (95% CI: 0.63, 1.29) for those without. The HR for women with family history who had H+ OC was 0.77 (95% CI: 0.45, 1.29) and 0.90 (95% CI: 0.63,1.29) for women without. This study suggests that the overall protective relationship observed between premenopausal hysterectomy with bilateral oophorectomy and breast-cancer specific mortality may be driven by a small subset of especially high-risk women. Citation Format: Mya L. Roberson, Whitney R. Robinson, Hazel B. Nichols, Andrew F. Olshan, Melissa A. Troester. Premenopausal oophorectomy and survival among women with breast cancer: Evidence of effect measure modification by family history status [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C052.

The Utility of Oncotype DX for Adjuvant Chemotherapy Treatment Decisions in Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative, Node-negative Breast Cancer.

IntroductionBreast cancer is the most common cancer diagnosis in the UK. Recently, there has been a reduction in breast cancer-specific mortality and recurrence attributed, in part, to the delivery of adjuvant chemotherapy. The National Institute for Health and Care Excellence (NICE) recommends the use of genetic profiling with Oncotype DX (ODX) to guide decisions to offer adjuvant chemotherapy after surgery in intermediate-risk early breast cancer patients. This study aimed to evaluate the utility of ODX testing in routine clinical practice in a National Health Service (NHS) hospital. MethodsConsecutive early breast cancer patients, identified through the multidisciplinary team (MDT) records, treated in our institution over 12 months (October 2017-September 2018) were included. PREDICT and Nottingham prognostic index (NPI) scores (from online clinicopathological recurrence risk tools) were calculated for each patient, and ODX data obtained through Genomic Health, Inc. (Redwood City, California). Patients were divided into two groups, those that underwent ODX testing (ODX group) and those that did not (non-ODX group). Descriptive statistics were used to analyse patient and tumour characteristics. The Gaussian distribution of each data set was assessed using the Anderson-Darling test. For comparisons between patient groups, the non-parametric equivalent of the two-tailed t-test (Mann-Whitney) was used. Dichotomous variables (e.g. chemotherapy decisions) were compared using chi-squared tests.ResultsOne-hundred thirty-three patients (mean age 62 years) treated for 152 early breast cancers, were included in the final analysis. Breast cancers in the ODX group were of greater median tumour size (24 vs 16 mm; P<0.0001) and higher median tumour grade (3 vs 2; P<0.0001). PREDICT scores (3 vs 1, P<0.0001) and NPI scores (3.40 vs 2.30, P<0.0001) for the ODX group were also significantly higher than the non-ODX group. A greater proportion of patients were offered chemotherapy in the ODX group (39.9% vs 6.9%, P<0.001). However, for the PREDICT-calculated intermediate-risk patients, ODX testing resulted in a lower proportion of patients being offered chemotherapy compared to the intermediate-risk patients who were not genetically profiled (54.5% vs 83.3%, P=0.3547), although this result was not statistically significant.ConclusionsPatients selected for ODX testing were younger, with significantly higher-grade and larger-sized tumours compared to patients not selected for genetic profiling. ODX testing significantly impacted the delivery of chemotherapy, as the recurrence score generated through ODX testing guided the final decision.

Premenopausal gynecologic surgery and survival among black and white women with breast cancer.

In the United States, hysterectomies and oophorectomies are frequently performed before menopause for benign conditions. The procedures are associated with reduced breast cancer-specific mortality among White women. The relationship between premenopausal gynecologic surgery and mortality in Black women with breast cancer is unknown. This investigation used incident invasive cases of breast cancer from Phases 1 and 2 of the Carolina Breast Cancer Study a population-based study that recruited Black and White women in North Carolina between 1993 and 2001. Premenopausal gynecologic surgery was operationalized in three categories: no surgery; hysterectomy with bilateral oophorectomy; hysterectomy with conservation of ≥ 1 ovary. Mortality was ascertained using the National Death Index, last updated in 2016. Multivariable-adjusted Cox Proportional Hazard Models were used to estimate the effect of premenopausal surgery on breast cancer-specific and all-cause mortality RESULTS: Hysterectomy with bilateral oophorectomy was associated with reduced breast cancer-specific mortality (HR 0.68; 95% CI 0.49, 0.96). White and Black women had a similar reduction in breast cancer-specific mortality. (HR among white: 0.66; 95% CI 0.43, 1.02), (HR among Black: 0.67; 95% CI 0.37, 1.21). There was a similar reduction in breast cancer-specific mortality following premenopausal, pre-diagnosis hysterectomy with bilateral oophorectomy across both Black and White women.

Abstract P4-02-02: Outcomes of diagnostic surgical biopsy in a population-based mammographic screening program

Abstract Background: Screening mammography allows earlier diagnosis of breast cancer resulting in reduced breast cancer specific mortality, and potentially reduced morbidity from less intense treatment. These benefits may be offset by investigation and treatment of lesions that are detected on screening but which are eventually found to be clearly benign, have uncertain malignant potential, or are malignant but pose no threat to the person during her natural life. Abnormalities detected on screening mammograms are recalled for further assessment. The outcomes of assessment may be confirmation of the absence suspicious findings. It may be a core biopsy is performed to clarify the nature of a persistently indeterminate or suspicious lesion. In cases when workup has neither diagnosed malignancy nor excluded its possibility, diagnostic surgical biopsy (DSB) is recommended. DSB of a lesion where final pathology is benign is a harm from a screening program. The benefit of DSB where a core needle biopsy (CNB) has shown a high-risk lesion is dependent on identifying more significant pathology than that of the CNB. Trials are currently recruiting which investigate a non-operative approach for DCIS, yet DSB is still standard of care for less significant/benign pathologies in much of the world. We aimed to determine the outcomes for patients recommended for DSB in a population-based mammographic screening program in order to identify situations in which this may safely be omitted. Methods: Ethics approval was obtained through Melbourne Health. Cases of DSB were reviewed from Northwest BreastScreen and Southern BreastScreen in Melbourne, Australia. Registry data was extracted including all patients where recommendation for DSB was made over a ten-year period (January 2004- December 2013). Patient demographics, imaging characteristics, core biopsy &amp; surgical pathology were reviewed manually from individual BreastScreen files. Data points were entered to an Excell database. We reviewed assessment reports, tabulated indications for DSB, and surgical pathology reports for final histopathology. Results: 1286 patients underwent DSB over the ten-year period. The overall upgrade rate to malignancy on DSB after non-malignant finding on CNB was 21.6% (14% to DCIS and 7.6% to invasive cancer). Atypical ductal hyperplasia (ADH) was the most common pathology identified on CNB generating recommendation for DSB. The overall upgrade rate for ADH was 31%, including 5.5% to invasive cancer, and 25.5% to DCIS. Further analysis of these ADH upgrades to DCIS revealed majority to low grade DCIS. Discussion: A minority of patients with high-risk lesions, detected through screening mammography, were upgraded to malignancy on DSB in this cohort. The psychological and cost-effectiveness implications of this low upgrade rate to significant, life-threatening pathologies warrants further investigation. Future recommendations may involve including lesions of uncertain malignant potential or “high-risk” lesions in prospective observation and/or chemoprevention trials. This series suggests there may not be benefit in earlier diagnosis of the malignancies associated with ADH. Our data may therefore allow identification of groups of women who could be safely managed with less intensive treatment. Citation Format: Keane HJ, Elder K, Mann GB. Outcomes of diagnostic surgical biopsy in a population-based mammographic screening program [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-02-02.

De novo vitamin D supplement use post-diagnosis is associated with breast cancer survival.

Experimental laboratory data have indicated a protective effect of vitamin D on breast cancer progression, while epidemiological evidence is growing. Using pharmacy claims data, this study investigates the association between vitamin D supplement use initiated after a breast cancer diagnosis and associated mortality. Women aged 50-80years with a record of invasive breast cancer were identified on the National Cancer Registry Ireland database (n = 5417). Initiation of de novo vitamin D post-diagnosis was identified from linked national prescription data (n = 2581, 49%). Multivariate Cox proportional hazards models were used to estimate adjusted HRs (95% CIs) for breast cancer-specific mortality. There was a 20% reduction in breast cancer-specific mortality in de novo vitamin D users (modelled as a time-varying variable) compared to non-users (HR 0.80; 95% CI 0.64-0.99, p = 0.048) and the reduction was greater at 49% (HR 0.51; 95% CI 0.34-0.74, p < 0.001), if vitamin D was initiated soon after the breast cancer diagnosis (within 6months). In this large national breast cancer cohort, de novo vitamin D use post-diagnosis was found to be associated with a reduction in breast cancer-specific mortality. Vitamin D, therefore, has the potential as a non-toxic and inexpensive agent to improve survival in breast cancer patients. Findings support the need for RCTs exploring the effect of vitamin D supplementation on breast cancer survival.

Resistance to discontinuing breast cancer screening in older women: A qualitative study.

Screening mammography is associated with reduced breast cancer-specific mortality; however, among older women, evidence suggests that the potential harms of screening may outweigh the benefits. We used a qualitative approach to examine the willingness of older women from different racial/ethnic groups to discontinue breast cancer screening. Women ≥70years of age who reported having a screening mammogram in the past 3years and/or reported that they intended to continue screening in the future were recruited for in-depth interviews. Participants who intended to continue screening were asked to describe how the following hypothetical scenarios would impact a decision to discontinue screening: health concerns or limited life expectancy, a physician's recommendation to discontinue, reluctance to undergo treatment, and recommendations from experts or governmental panels to stop screening. Semi-structured, face-to-face interviews were audio-recorded. Data coding and analysis followed inductive and deductive approaches. Regardless of the scenario, participants (n=29) expressed a strong intention to continue screening. Based on the hypothetical physician recommendations, intentions to continue screening appeared to remain strong. They did not envision a change in their health status that would lead them to discontinue screening and were skeptical of expert/government recommendations. There were no differences observed according to age, race/ethnicity, or education. Among older women who planned to continue screening, intentions to continue breast cancer screening appear to be highly resilient and resistant to recommendations from physicians or expert/government panels.

Abstract ES1-2: Guidelines for postmastectomy radiotherapy

Abstract A joint panel of the American Society of Clinical Oncology (ASCO), American Society for Radiation Oncology (ASTRO), and Society of Surgical Oncology (SSO) convened in 2015 to develop an update of the prior ASCO guideline (J Clin Oncol 2001;19:1539-1569) concerning the use of postmastectomy radiation therapy (PMRT). This effort focused on common scenarios where there have been substantial controversy. Their conclusions and supporting evidence have been published (J Clin Oncol 2016;34:4431-4442). The Panel unanimously agreed that PMRT reduces the risks of local-regional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with 1-3 positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. The Panel however could not find sufficient evidence to recommend a specific formula or method of how to combine clinical, pathologic, and biologic data to calculate the risk of LRF. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT or not requires a great deal of clinical judgement. The Panel agreed clinicians making such recommendations for an individual patient should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase the risks of complications from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the Panel recommended that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know that additional axillary nodes are involved. Patients with axillary nodal involvement following neoadjuvant systemic therapy should receive PMRT. The role of PMRT in other patients with clinical Stage I or II breast cancer is uncertain. Finally, the Panel recommended that radiation therapy generally be given to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast when PMRT is used. However, there may be subgroups that will have limited, if any, benefits from treating both these nodal areas compared to treating only one of them or, perhaps, treating only the chest wall or reconstructed breast. There is insufficient evidence at this time to define such subgroups in detail. This lecture will address selected elements of the data leading to the Panel's decisions. Citation Format: Recht A. Guidelines for postmastectomy radiotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES1-2.

Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis.

Purpose: Breast cancer is among the leading causes of cancer-related death; discovery of novel prognostic markers is needed to improve outcomes. Combining systems biology and epidemiology, we investigated miRNA-associated genes and breast cancer survival in a well-characterized population-based study.Experimental Design: A recently developed algorithm, ActMiR, was used to identify key miRNA "activities" corresponding to target gene degradation, which were predictive of breast cancer mortality in published databases. We profiled miRNA-associated genes in tumors from our well-characterized population-based cohort of 606 women with first primary breast cancer. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals (CI), after 15+ years of follow-up with 119 breast cancer-specific deaths.Results: miR-500a activity was identified as a key miRNA for estrogen receptor-positive breast cancer mortality using public databases. From a panel of 161 miR-500a-associated genes profiled, 73 were significantly associated with breast cancer-specific mortality (FDR < 0.05) in our population, among which two clusters were observed to have opposing directions of association. For example, high level of SUSD3 was associated with reduced breast cancer-specific mortality (HR = 0.3; 95% CI, 0.2-0.4), whereas the opposite was observed for TPX2 (HR = 2.7; 95% CI, 1.8-3.9). Most importantly, we identified set of genes for which associations with breast cancer-specific mortality were independent of known prognostic factors, including hormone receptor status and PAM50-derived risk-of-recurrence scores. These results are validated in independent datasets.Conclusions: We identified novel markers that may improve prognostic efficiency while shedding light on molecular mechanisms of breast cancer progression. Clin Cancer Res; 24(3); 581-91. ©2017 AACR.

Pre-diagnostic statin use, lymph node status and mortality in women with stages I\u2013III breast cancer

Background:Recent meta-analyses suggest that pre-diagnostic statin use is associated with reduced breast cancer-specific mortality. Studies have shown that high breast tumour expression of the statin target (3-hydroxy-3-methylglutaryl coenzyme-A reductase) is associated with lymph-node negative cancer. Therefore, we examined the association between pre-diagnostic statin use and; lymph node status, breast cancer-specific and all-cause mortality.Methods:Women with stages I–III breast cancer were identified from the National Cancer Registry of Ireland (N=6314). Pre-diagnostic statin users were identified from linked prescription claims data (N=2082). Relative risks were estimated for associations between pre-diagnostic statin use and lymph node status. Hazard ratios (HR) were estimated for associations between pre-diagnostic statin use and breast cancer-specific and all-cause mortality.Results:Pre-diagnostic statin use was not associated with lymph node negative status at diagnosis. In multivariate analyses, pre-diagnostic statin use was associated with reduced all-cause (HR 0.78 95% confidence interval (CI) 0.69, 0.89) and breast cancer-specific mortality (HR 0.81 95% CI 0.68, 0.96). This reduction in cancer-specific mortality was greatest in statin-users with oestrogen (ER) receptor-positive tumours (HR 0.69 95% CI 0.55, 0.85).Conclusion:Patients with pre-diagnostic statin exposure had a significant reduction in breast cancer-specific mortality, which was even more pronounced in women with ER+ tumours.

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update.

Purpose A joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT). Methods A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. Recommendations The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update

A recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data. The panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Postmastectomy Radiotherapy: An American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology Focused Guideline Update

PurposeA joint American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology panel convened to develop a focused update of the American Society of Clinical Oncology guideline concerning use of postmastectomy radiotherapy (PMRT).MethodsA recent systematic literature review by Cancer Care Ontario provided the primary evidentiary basis. The joint panel also reviewed targeted literature searches to identify new, potentially practice-changing data.RecommendationsThe panel unanimously agreed that available evidence shows that PMRT reduces the risks of locoregional failure (LRF), any recurrence, and breast cancer mortality for patients with T1-2 breast cancer with one to three positive axillary nodes. However, some subsets of these patients are likely to have such a low risk of LRF that the absolute benefit of PMRT is outweighed by its potential toxicities. In addition, the acceptable ratio of benefit to toxicity varies among patients and physicians. Thus, the decision to recommend PMRT requires a great deal of clinical judgment. The panel agreed clinicians making such recommendations for individual patients should consider factors that may decrease the risk of LRF, attenuate the benefit of reduced breast cancer-specific mortality, and/or increase risk of complications resulting from PMRT. When clinicians and patients elect to omit axillary dissection after a positive sentinel node biopsy, the panel recommends that these patients receive PMRT only if there is already sufficient information to justify its use without needing to know additional axillary nodes are involved. Patients with axillary nodal involvement after neoadjuvant systemic therapy should receive PMRT. The panel recommends treatment generally be administered to both the internal mammary nodes and the supraclavicular-axillary apical nodes in addition to the chest wall or reconstructed breast.

Statin use and breast cancer survival: a nationwide cohort study in Scotland.

BackgroundPreclinical evidence suggests that statins could delay cancer progression. Previous epidemiological findings have been inconsistent and some have been limited by small sample sizes, as well as certain time-related biases. This study aimed to investigate whether breast cancer patients who were exposed to statins had reduced breast cancer-specific mortality.MethodsWe conducted a retrospective cohort study of 15,140 newly diagnosed invasive breast cancer patients diagnosed from 2009 to 2012 within the Scottish Cancer Registry. Dispensed medication usage was obtained from linkages to the Scottish Prescribing Information System and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Using time-dependent Cox regression models, hazard ratios (HR) and 95 % confidence intervals (CI) were calculated for the association between post-diagnostic exposure to statins (including simvastatin) and breast cancer-specific mortality. Adjustments were made for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of aspirin.ResultsA total of 1,190 breast cancer-specific deaths occurred up to January 2015. Overall, after adjustment for potential confounders, there was no evidence of an association between statin use and breast cancer-specific death (adjusted HR 0.93, 95 % CI 0.77, 1.12). No significant associations were observed in dose–response analyses or in analysis of all-cause mortality. For simvastatin use specifically, a weak non-significant reduction in breast cancer-specific mortality was observed compared to non-users (adjusted HR 0.89, 95 % CI 0.73, 1.08). Statin use before diagnosis was weakly associated with a reduction in breast cancer-specific mortality (adjusted HR 0.85, 95 % CI 0.74, 0.98).ConclusionOverall, we found little evidence of a protective association between post-diagnostic statin use and cancer-specific mortality in a large nation-wide cohort of breast cancer patients. These findings will help inform the decision whether to conduct randomised controlled trials of statins as an adjuvant treatment in breast cancer.

De novo post-diagnosis statin use, breast cancer-specific and overall mortality in women with stage I–III breast cancer

Background:Prior evidence suggests a role for statins in the management of cancer. However, the benefit of statin use in the adjuvant setting remains uncertain. This study investigates associations between statin use initiated after a breast cancer diagnosis and mortality.Methods:Women with stage I–III breast cancer were identified from the National Cancer Registry of Ireland (N=4243). Post-diagnostic statin initiators were identified from pharmacy claims data (N=837). Multivariate models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between de novo statin use and mortality.Results:The median duration of statin use was 6.7 years. No association was found between post-diagnostic statin use and breast cancer-specific (HR 0.88, 95% CI 0.66, 1.17) or all-cause mortality (HR 1.00, 95% CI 0.82, 1.21).Conclusions:The results from our study suggest that initiating statin use after a diagnosis of stage I–III breast cancer is not associated with a reduction in breast cancer-specific mortality.

De Novo Post-Diagnosis Aspirin Use and Mortality in Women with Stage I-III Breast Cancer.

Aspirin use has been associated with significant reductions in breast cancer-related mortality in some observational studies. However, these studies included women who initiated aspirin use before breast cancer diagnosis. It is unclear whether initiating aspirin use after diagnosis is associated with similar reductions in mortality. This study investigates associations between de novo post-diagnostic aspirin use and all cause, breast cancer-specific mortality. Women, ages 50 to 80, with a diagnosis of stage I-III breast cancer were identified from Ireland's National Cancer Registry (N = 4,540). Initiation of de novo post-diagnostic aspirin use was identified from linked national prescription refill data (N = 764). Adjusted HRs were estimated for associations between de novo aspirin use and all-cause, breast cancer-specific mortality. The median time from diagnosis to aspirin initiation was 1.8 years. The mean number of days' supply of aspirin received was 631, and 95% of users were taking less than 150 mg/d. We found no association between de novo aspirin use and breast cancer-specific mortality [HR, 0.98; 95% confidence interval (CI), 0.74-1.30]. Similar null associations were found in women taking aspirin at high-intensity (HR, 1.03; 95% CI, 0.72-1.47) and women initiating use in the 1.5 years after diagnosis (HR, 1.04; 95% CI, 0.77-1.40). There was no effect modification by estrogen (Pinteraction = 0.81) or progesterone (Pinteraction = 0.41) receptor status. Initiating aspirin use after a breast cancer diagnosis was not associated with a reduction in breast cancer-specific mortality. On the basis of our findings, we suggest that a clearer understanding of aspirin's mechanism of action is needed to help inform the design of future studies in breast cancer.

Abstract P6-10-04: Statins and breast cancer stage and mortality in the Women's Health Initiative cohort

Abstract Background: Statins are the most widely prescribed cholesterol-lowering drugs in the United States, with approximately 25% of US adults using statins by 2008. The anti-carcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to ‘stage migration’ with statin users more likely diagnosed with early rather than late stage cancer. We evaluated the effects of statins on breast cancer stage migration and breast cancer-specific mortality in the Women’s Health Initiative (WHI) Clinical Trial and Observational Study. Methods: The study population included 128,675 postmenopausal women aged 50 to 79 years, with 7,883 newly-diagnosed pathologically-confirmed cases of in situ (19%), local stage (61%), regional stage (19%) and distant stage (1%) breast cancer and 401 deaths due to breast cancer after an average of 11.5 (SD=3.7) years of follow-up. To reduce the possibility of detection bias, we excluded women who did not report a mammogram within 5 years of study entry, and who had no health insurance or medical care provider (n=28,237). Stage was coded using criteria implemented in the Surveillance, Epidemiology and End Results Program and stratified into early stage (in situ and local) vs. late stage (regional and distant). Information on statin use prior to breast cancer diagnosis was collected at baseline and years one, three, six, and nine years post-baseline. Self- and interviewer-administered questionnaires were used to collect risk factor information. Cause of death was based on medical record review by physician adjudicators. Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) to evaluate the relationship between statin use as a time-dependent exposure and diagnosis of late stage breast cancer and breast cancer-specific mortality adjusting for important confounders. For these models, participants who had early stage breast cancer or who died during follow-up were censored at time of diagnosis or death, respectively. We also evaluated the effect of statins stratified by estrogen receptor (ER) status. Statistical tests were two-sided. Results: Statins were used by 10,474 women (8%) at baseline. In the multivariable-adjusted time-dependent model, statin use was associated with a marginal reduction in risk of late stage breast cancer (HR 0.84, 95% CI: 0.70-1.02, p=0.082) and a reduction in risk of late stage estrogen receptor positive breast cancer (HR 0.79, 95% CI: 0.63-0.99, p=0.044). Statin use was also associated with a marginal reduction in breast cancer-specific mortality although it did not reach statistical significance (HR 0.59, 95% CI: 0.32-1.06, p=0.075). Conclusions: In the WHI, statin use was associated with a modest reduction in risk of late stage estrogen positive breast cancer and a non-significant decrease in breast cancer mortality. We are currently performing sensitivity analyses on these models. Studies using other large data sets with longer follow-up and information on cancer-directed therapy are needed to further evaluate this possible association. Citation Format: Monica P Arun, Pinkal Desai, Amy Lehman, Marilyn L Kwan, JoAnn E Manson, Sayeh Lavasani, Sylvia Wasswertheil-Smoller, Gloria E Sarto, Meryl S LeBoff, Jane Cauley, Michele L Cote, Jennifer Beebe-Dimmer, Allison Jay, Rowan T Chlebowski, Michael S Simon. Statins and breast cancer stage and mortality in the Women's Health Initiative cohort [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-10-04.