Breast Cancer Systemic Treatments and Upper Limb Lymphedema: A Risk-Assessment Platform Encompassing Tumor-Specific Pathological Features Reveals the Potential Role of Trastuzumab

Breast cancer related lymphedema (BCRL) is frequent but strategies for an individualized risk assessment are lacking. We aimed to define whether tumor-specific pathological features, coupled with clinical and therapeutic data, could help identify patients at risk. Data from 368 patients with node-positive breast cancers were retrospectively collected, including 75 patients with BCRL (0.4–25.6 years follow-up). BCRL was assessed during the standard follow-up oncology visits using the circumferential measurement. Clinicopathologic and therapeutic factors associated with BCRL were integrated into a Cox proportional hazards regression model. Lymphovascular invasion (LVI) was more common in BCRL patients (n = 33, 44% vs. n = 85, 29%, p = 0.01), akin extra nodal extension (ENE) of the metastasis (n = 57, 76% vs. n = 180, 61%, p = 0.02). Sentinel lymph node excision without axillary dissection and extra-axillary radiotherapy were BCRL-unrelated. A higher number of BCRL-positive patients were treated with taxane-based chemotherapy with or without trastuzumab, compared to BCRL-negative patients (p < 0.01). Treatment with trastuzumab and/or taxanes, adjusted for systemic infections, laterality, therapy, and pathological features (i.e., LVI and ENE), had a significant impact in BCRL-free survival (p < 0.01). This work offers new insights on BCRL risk stratification, where the integration of clinical, therapeutic, and tumor-specific pathological data suggests a possible role of anti-human epidermal growth factor receptor 2 (HER2) therapy in BCRL pathogenesis.

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Association between overall diet quality and postmenopausal breast cancer risk in five Finnish cohort studies

Scientific Reports ◽

10.1038/s41598-021-95773-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Satu Männistö ◽

Kennet Harald ◽

Tommi Härkänen ◽

Mirkka Maukonen ◽

Johan G. Eriksson ◽

...

Keyword(s):

Breast Cancer ◽

Diet Quality ◽

Proportional Hazards ◽

Postmenopausal Breast Cancer ◽

Healthy Eating Index ◽

Cox Proportional Hazards ◽

Healthy Diet ◽

Food Culture ◽

Alternative Healthy Eating Index

AbstractThere is limited evidence for any dietary factor, except alcohol, in breast cancer (BC) risk. Therefore, studies on a whole diet, using diet quality indices, can broaden our insight. We examined associations of the Nordic Diet (mNDI), Mediterranean diet (mMEDI) and Alternative Healthy Eating Index (mAHEI) with postmenopausal BC risk. Five Finnish cohorts were combined including 6374 postmenopausal women with dietary information. In all, 8–9 dietary components were aggregated in each index, higher total score indicating higher adherence to a healthy diet. Cox proportional hazards regression was used to estimate the combined hazard ratio (HR) and 95% confidence interval (CI) for BC risk. During an average 10-year follow-up period, 274 incident postmenopausal BC cases were diagnosed. In multivariable models, the HR for highest vs. lowest quintile of index was 0.67 (95 %CI 0.48–1.01) for mNDI, 0.88 (0.59–1.30) for mMEDI and 0.89 (0.60–1.32) for mAHEI. In this combined dataset, a borderline preventive finding of high adherence to mNDI on postmenopausal BC risk was found. Of the indices, mNDI was more based on the local food culture than the others. Although a healthy diet has beneficially been related to several chronic diseases, the link with the etiology of postmenopausal BC does not seem to be that obvious.

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Supper Timing and Cardiovascular Mortality: The Japan Collaborative Cohort Study

Nutrients ◽

10.3390/nu13103389 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3389

Author(s):

Jingyun Tang ◽

Jia-Yi Dong ◽

Ehab S. Eshak ◽

Renzhe Cui ◽

Kokoro Shirai ◽

...

Keyword(s):

Hemorrhagic Stroke ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Stroke Mortality ◽

Hazard Ratios ◽

Risk Of Mortality ◽

Increased Risk ◽

Study Participants

Evidence on the role of supper timing in the development of cardiovascular disease (CVD) is limited. In this study, we examined the associations between supper timing and risks of mortality from stroke, coronary heart disease (CHD), and total CVD. A total of 28,625 males and 43,213 females, aged 40 to 79 years, free from CVD and cancers at baseline were involved in this study. Participants were divided into three groups: the early supper group (before 8:00 p.m.), the irregular supper group (time irregular), and the late supper group (after 8:00 p.m.). Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for stroke, CHD, and total CVD according to the supper time groups. During the 19-year follow-up, we identified 4706 deaths from total CVD. Compared with the early supper group, the multivariable HR of hemorrhagic stroke mortality for the irregular supper group was 1.44 (95% confidence interval [CI]: 1.05–1.97). There was no significant association between supper timing and the risk of mortality from other types of stroke, CHD, and CVD. We found that adopting an irregular supper timing compared with having dinner before 8:00 p.m. was associated with an increased risk of hemorrhagic stroke mortality.

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Diabetes, Metformin, and Breast Cancer in Postmenopausal Women

Journal of Clinical Oncology ◽

10.1200/jco.2011.39.7505 ◽

2012 ◽

Vol 30 (23) ◽

pp. 2844-2852 ◽

Cited By ~ 121

Author(s):

Rowan T. Chlebowski ◽

Anne McTiernan ◽

Jean Wactawski-Wende ◽

JoAnn E. Manson ◽

Aaron K. Aragaki ◽

...

Keyword(s):

Breast Cancer ◽

Postmenopausal Women ◽

Cancer Incidence ◽

Proportional Hazards ◽

Breast Cancer Incidence ◽

Cox Proportional Hazards ◽

Diabetes Incidence ◽

Breast Cancers ◽

Cancer Risk Factors ◽

Cancer Management

Purpose Emerging evidence suggests that metformin may reduce breast cancer incidence, but reports are mixed and few provide information on tumor characteristics. Therefore, we assessed associations among diabetes, metformin use, and breast cancer in postmenopausal women participating in Women's Health Initiative clinical trials. Patients and Methods In all, 68,019 postmenopausal women, including 3,401 with diabetes at study entry, were observed over a mean of 11.8 years with 3,273 invasive breast cancers diagnosed. Diabetes incidence status was collected throughout follow-up, with medication information collected at baseline and years 1, 3, 6, and 9. Breast cancers were confirmed by review of central medical records and pathology reports. Cox proportional hazards regression, adjusted for breast cancer risk factors, compared breast cancer incidence in women with diabetes who were metformin users or nonusers with breast cancer incidence in women without diabetes. Results Compared with that in women without diabetes, breast cancer incidence in women with diabetes differed by diabetes medication type (P = .04). Women with diabetes receiving medications other than metformin had a slightly higher incidence of breast cancer (hazard ratio [HR], 1.16; 95% CI, 0.93 to 1.45), and women with diabetes who were given metformin had lower breast cancer incidence (HR, 0.75; 95% CI, 0.57 to 0.99). The association was observed for cancers positive for both estrogen receptor and progesterone receptor and those that were negative for human epidermal growth factor receptor 2. Conclusion Metformin use in postmenopausal women with diabetes was associated with lower incidence of invasive breast cancer. These results can inform future studies evaluating metformin use in breast cancer management and prevention.

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Early breast cancer: evaluation of the prognostic role of the site of the primary tumor.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.4.1363 ◽

1998 ◽

Vol 16 (4) ◽

pp. 1363-1366 ◽

Cited By ~ 67

Author(s):

R Zucali ◽

L Mariani ◽

E Marubini ◽

R Kenda ◽

L Lozza ◽

...

Keyword(s):

Breast Cancer ◽

Early Breast Cancer ◽

Distant Metastases ◽

Breast Cancers ◽

Prognostic Role ◽

Long Term Follow Up ◽

Internal Mammary

PURPOSE The prognostic role of the site of the primary breast cancer has not been clarified. This study aimed to gather more information about this issue from a large series of patients with long-term follow-up data. PATIENTS AND METHODS Data from 2,396 patients treated for early breast cancer with a conservative approach were reviewed (1973 to 1989). In 1,619 patients, the tumor had a lateral site, while in 777 cases, it was situated in the internal/central quadrants. The characteristics of the two groups were well balanced, apart from axillary nodal metastases, which were more frequent for lateral tumors (38.1% v 26.3%). RESULTS Analysis of distant metastases indicated that the regression coefficient associated with tumor site was significant and the hazards ratio estimate was 1.291, which indicates the risk of distant metastases was increased by approximately 30% for internal/central tumors. The analysis of overall survival yielded a significant coefficient and a hazards ratio of 1.192, which indicates an approximately 20% increase of mortality for internal/central tumors. CONCLUSION Early breast cancers situated in central/ internal quadrants have a worse prognosis compared with those in lateral quadrants, in terms of distant metastases and survival. Irradiation of the internal mammary chain for internal/medial tumors could be suggested, but, to date, the therapeutic strategy is still controversial.

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P2277Utility of cardiovascular implantable electronic device (CIED)-derived patient activity, a novel digital biomarker, to predict inappropriate therapy

European Heart Journal ◽

10.1093/eurheartj/ehz748.0754 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Rosero ◽

P Jones ◽

I Goldenberg ◽

W Zareba ◽

K Stein ◽

...

Keyword(s):

Proportional Hazards ◽

Electronic Device ◽

Cox Proportional Hazards ◽

Inappropriate Therapy ◽

Activity Data ◽

Proportional Hazards Regression ◽

Kaplan Meier ◽

Cardiovascular Implantable Electronic Device

Abstract Background The role of cardiovascular implantable electronic device (CIED)-derived activity to predict inappropriate implantable cardioverter-defibrillator (ICD) therapy is not known. The Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy (MADIT-RIT) enrolled 1500 patients with contemporary indication for an ICD or a CRT-D. We aimed to identify whether activity, as a digital biomarker, predicted inappropriate therapy. Methods In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily. CIED-derived activity was averaged for the first 30 days following randomization and utilized in this study to predict inappropriate therapy post- 30-day. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models were used to evaluate first inappropriate therapy by 30-day CIED-derived patient activity quintiles, and by 30-day device derived patient activity as a continuous measurement. Results There were a total of 1463 patients with activity data available (90%), 135 patients received at least one inappropriate therapy during the post-30 day follow-up period. Patients in the highest quintile (Q5) of CIED-derived activity (more active) were younger, more often males and more likely to have had a prior ablation of an atrial arrhythmia. Patients in the highest quintile of 30-day CIED-derived median activity had the highest risk of receiving inappropriate therapy, 21% at 2 years as compared 7–11% in the other four quintiles (Figure, p<0.001 for the overall duration). Patients with the highest level of 30-day median patient activity (Q5) had 1.75 times higher risk of any inappropriate therapy as compared with lower levels of activity, Q1-Q4 (HR=1.75, 95% CI: 1.23–2.50, p<0.002). Each 10% increase in CIED-derived 30-day median patient activity was associated with a significant, 73% increase in risk of receiving inappropriate therapy (HR=1.73, 95% CI: 1.17–2.54, p=0.005). Patients in the highest quintile for activity had a 68% increase in the risk of SVT excluding atrial fibrillation, atrial flutter or atrial tachycardia (HR=1.69, 95% CI: 1.26–2.25, p=0.004), despite 96% receiving beta-blocker medications. Inappropriate ICD Therapies by Activity Conclusions CIED-derived 30-day median patient activity predicted subsequent inappropriate therapy in ICD and CRT-D patients enrolled in MADIT-RIT. Patients with high levels of 30-day CIED-derived median patient activity were at a significantly higher risk of receiving inappropriate therapy. Activity, as a digital biomarker, may have utility in predicting and managing the risk of inappropriate therapy in this population. Acknowledgement/Funding Boston Scientific

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Dietary Antioxidant Vitamins and Minerals and Breast Cancer Risk: Prospective Results from the SUN Cohort

Antioxidants ◽

10.3390/antiox10030340 ◽

2021 ◽

Vol 10 (3) ◽

pp. 340

Author(s):

Cesar I. Fernandez-Lazaro ◽

Miguel Ángel Martínez-González ◽

Inmaculada Aguilera-Buenosvinos ◽

Alfredo Gea ◽

Miguel Ruiz-Canela ◽

...

Keyword(s):

Breast Cancer ◽

Vitamin E ◽

Proportional Hazards ◽

Natural Antioxidants ◽

Cox Proportional Hazards ◽

University Graduates ◽

Inverse Association ◽

The Sun ◽

Dietary Intakes

There is growing interest in natural antioxidants and their potential effects on breast cancer (BC). Epidemiological evidence, however, is inconsistent. We prospectively evaluated the association between dietary intake of vitamins A, C, and E, selenium, and zinc and BC among 9983 female participants from the SUN Project, a Mediterranean cohort of university graduates. Participants completed a food frequency questionnaire at baseline, and biennial follow-up information about incident BC diagnosis was collected. Cases were ascertained through revision of medical charts and consultation of the National Death Index. Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CI). During an average follow-up of 11.3 years, 107 incident BC cases were confirmed. The multivariable HRs (95% CI) for BC comparing extreme tertiles of energy-adjusted dietary intakes were 1.07 (0.64–1.77; Ptrend = 0.673) for vitamin A, 1.00 (0.58–1.71; Ptrend = 0.846) for vitamin C, 0.92 (0.55–1.54; Ptrend = 0.728) for vitamin E, 1.37 (0.85–2.20; Ptrend = 0.135) for selenium, and 1.01 (0.61–1.69; Ptrend = 0.939) for zinc. Stratified analyses showed an inverse association between vitamin E intake and postmenopausal BC (HRT3 vs. T1 = 0.35; 95% CI, 0.14–0.86; Ptrend = 0.027). Our results did not suggest significant protective associations between dietary vitamins A, C, and E, selenium, or zinc and BC risk.

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The Role of Leisure Activities as Markers of Cognitive Reserve on Dementia Risk in English Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.2297 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 664-664

Author(s):

Pamela Almeida Meza ◽

Andrew Steptoe ◽

Dorina Cadar

Keyword(s):

Marital Status ◽

Cognitive Reserve ◽

Proportional Hazards ◽

Leisure Activities ◽

Cox Proportional Hazards ◽

Dementia Risk ◽

The Social ◽

Social Type

Abstract We examined the frequency of participation in cognitive and social type of leisure activities in association with dementia risk over 15 years of follow-up in 12,280 participants aged 50+ from the English Longitudinal Study of Ageing. Cox proportional hazards regression models were used to estimate the hazard of dementia in relation to the cognitive and social type of leisure activities as well as their interactions with sex and marital status. Medium and higher levels of engagement in cognitive leisure activities were associated with a lower risk of dementia. An analysis of the social type of leisure activities showed a similar pattern with protection for higher levels of engagement in a model adjusted for sex and marital status but further explained by wealth. This study shows a reduced risk of dementia for individuals with higher levels of engagement in cognitively stimulating activities, that may preserve cognitive reserve until later in life.

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Adjuvant endocrine monotherapy (ET) versus adjuvant breast radiation (RT) alone in healthy older women with stage I, estrogen receptor-positive (ER+) breast cancer: An analysis of the National Cancer Database (NCDB).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.519 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 519-519

Author(s):

Anthony H. Bui ◽

Manjeet Chadha ◽

Theresa H. Shao ◽

Naamit K. Gerber ◽

Sarah P. Cate ◽

...

Keyword(s):

Breast Cancer ◽

Older Women ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Stage I ◽

Nccn Guidelines ◽

Treatment Groups ◽

Distant Relapse ◽

Demographic Covariates

519 Background: The NCCN guidelines state that breast RT may be omitted in patients > 70 years of age with ER+, clinically node-negative, T1 breast cancer (BC) who receive adjuvant ET. Available data on older patients notes that local relapses are the most frequent site of failure, and distant relapse rates are low. The side effects of ET are not inconsequential and negatively affect QOL. The objectives of this study are to examine clinical outcomes including overall survival (OS) in women ≥70 years of age treated by lumpectomy(L)+ET and L+RT in the NCDB. Methods: The 2004-2013 NCDB includes 76,431 women ≥70 years with ER+ stage I BC who underwent L, and had a minimum one year follow up. Women who received no adjuvant therapy, both ET+RT, or any chemotherapy were excluded. To limit the analysis to healthy women, we excluded subjects with a Charlson comorbidity index > 0. We identified 24,572 patients who received either adjuvant ET monotherapy or adjuvant RT alone. Among these, 46% (11,313) received ET and 54% (13,259) breast RT. Overall median follow up was 57 months (range: 12-143 months). Analysis of OS between the 2 treatment groups was performed using Kaplan-Meier statistics and Cox proportional hazards regression; propensity weighting was used to balance covariates across the 2 treatment groups. Results: After propensity weighting, demographic covariates including age, race, insurance, and facility type were balanced between the 2 treatment groups. The median OS for ET was 125.9 months (95% CI 120.1-131.8), and 127.2 months for RT (95% CI 124.5-131.7) (p < 0.0001). The weighted hazard of death was 11.7% less in women receiving RT compared to ET (HR 0.883, 95% CI 0.834-0.936, p < 0.0001). Conclusions: To our knowledge, this is the first large study comparing RT and ET monotherapy in healthy older women with stage I, ER+ BC. The OS with RT alone is not inferior to ET alone, and in this study population is noted to be better. While this analysis has various limitations not dissimilar from other NCDB database studies, our observations are encouraging and warrant further research with prospective studies.

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Use of postmenopausal hormone therapies and risk of histology- and hormone receptor-defined breast cancer: results from a 15-year prospective analysis of NIH-AARP cohort

Breast Cancer Research ◽

10.1186/s13058-020-01365-9 ◽

2020 ◽

Vol 22 (1) ◽

Author(s):

Shao-Ming Wang ◽

Ruth M. Pfeiffer ◽

Gretchen L. Gierach ◽

Roni T. Falk

Keyword(s):

Breast Cancer ◽

Hormone Receptor ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Estrogen Plus Progestin ◽

Continued Use ◽

Progestin Therapy

Abstract Background Menopausal hormone therapy (MHT) increases breast cancer (BC) risk, but cohort studies largely consider use only at enrollment. Evidence is limited on how changes in MHT use alter the magnitude of risk, and whether risk varies between invasive and in situ cancer, by histology or by hormone receptor status. Methods We investigated the roles of estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT) on BC risk overall, by histology and estrogen receptor (ER) and progesterone receptor (PR) status, and on incidence of in situ disease, in the NIH-AARP cohort. Participants included 118,760 postmenopausal women (50–71 years), of whom 63.5% (n = 75,398) provided MHT use information at baseline in 1996 and in a follow-up survey in 2004, subsequent to the dissemination in 2002 of the Women’s Health Initiative trial safety concerns regarding EPT. ET analyses included 50,476 women with hysterectomy (31,439 with follow-up data); EPT analyses included 68,284 women with intact uteri (43,959 with follow-up data). Adjusted hazard ratios (HRs) were estimated using Cox proportional hazards models using age as the time metric with follow-up through 2011. Results Eight thousand three hundred thirty-three incident BC cases were accrued, 2479 in women with follow-up data. BC risk was not elevated in current ET users at baseline (HR = 1.05, 95% confidence interval [CI] CI = 0.95–1.16) but was higher in women continuing use through 2004 (HR = 1.35, 95% CI = 1.04–1.75). Ever EPT use at baseline was associated with elevated BC risk overall (HR = 1.54 (1.44–1.64), with a doubling in risk for women with 10 or more years of use, for in situ disease, and across subtypes defined by histology and ER/PR status (all p < 0.004). Risk persisted in women who continued EPT through 2004 (HR = 1.80, 95% CI = 1.39–2.32). In contrast, no association was seen in women who discontinued EPT before 2004 (HR = 1.14, 95% CI = 0.99–1.30). Conclusions ET use was not associated with BC risk in this cohort, although excess risk was suggested in women who continued use through 2004. EPT use was linked to elevated in situ and invasive BC risk, and elevated risk across invasive BC histologic and hormone receptor-defined subtypes, with the highest risk for women who continued use through the 2004 follow-up survey.

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Exploring the Role of Breast Density on Cancer Prognosis among Women Attending Population-Based Screening Programmes

Journal of Oncology ◽

10.1155/2019/1781762 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Laia Domingo ◽

Maria Sala ◽

Javier Louro ◽

Marisa Baré ◽

Teresa Barata ◽

...

Keyword(s):

Breast Cancer ◽

Breast Density ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

High Density ◽

Cancer Prognosis ◽

Low Density ◽

Risk Of Death

Background. Our aim was to assess the role of breast density on breast cancer mortality and recurrences, considering patient and tumour characteristics and the treatments received among women attending population-based screening programmes. Methods. We conducted a retrospective cohort study among women aged 50–69 years attending population-based screening programmes, diagnosed with invasive breast cancer between 2000 and 2009, and followed up to 2014. Breast density was categorised as low density (≤25% dense tissue), intermediate density (25–50%), and high density (≥50%). Cox proportional hazards regression models were fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) for death and recurrences, adjusting by patient characteristics, mode of detection (screen-detected vs. interval cancer), and tumour features. Results. The percentage of deaths and recurrences was higher among women with intermediate- and high-density breasts than among women with low-density breasts (p=0.011 for death; p=0.037 for recurrences). Adjusted Cox proportional hazards regression models revealed that women with intermediate- and high-density breasts had a higher risk of death than women with low-density breasts, being statistically significant for intermediate densities (aHR = 2.19 [95% CI: 1.16–4.13], aHR = 1.44 [95% CI: 0.67–3.1], respectively). No association was found between breast density and recurrences. Conclusions. Breast density was associated with a higher risk of death, but not of recurrences, among women participating in breast cancer screening. These findings reinforce the need to improve screening sensitivity among women with dense breasts and to routinely assess breast density, not only for its role as a risk factor for breast cancer but also for its potential influence on cancer prognosis.

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