Obesity and menopausal status impact the features and molecular phenotype of invasive lobular breast cancer

Abstract Purpose We investigated the relationship between obesity, menopausal status, and invasive lobular carcinoma (ILC), the second most common histological subtype of breast cancer. Specifically, we evaluated the association between body mass index (BMI), metabolic syndrome, the 21-gene Oncotype Recurrence Score (Oncotype RS), and pathological features in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2-negative ILC. Methods The study cohort included 491 patients from a prospectively maintained institutional database consisting of patients with stage I-III, HR-positive ILC who underwent surgical treatment between 1996 and 2019. Results Contrary to our expectations, we found that lower BMI was significantly associated with having higher Oncotype RS (18.9% versus 4.8%, p = 0.028) in post-menopausal patients, but was not related to tumor characteristics in pre-menopausal patients. Multivariate network analyses suggested a strong relationship between post-menopausal status itself and tumor characteristics, with lesser influence of BMI. Conclusion These findings provide further insight into the recently appreciated heterogeneity within ILC and support the need for further investigation into the drivers of this disease and tailored treatment strategies.

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Adjuvant Hormonotherapy and Cardiovascular Risk in Post-Menopausal Women with Breast Cancer: A Large Population-Based Cohort Study

Cancers ◽

10.3390/cancers13092254 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2254

Author(s):

Matteo Franchi ◽

Roberta Tritto ◽

Luigi Tarantini ◽

Alessandro Navazio ◽

Giovanni Corrao

Keyword(s):

Breast Cancer ◽

Heart Failure ◽

Adjuvant Therapy ◽

Large Population ◽

Positive Association ◽

Population Based ◽

Study Cohort ◽

Increased Risk ◽

Post Menopausal ◽

New Diagnosis

Background: Whether aromatase inhibitors (AIs) increase the risk of cardiovascular (CV) events, compared to tamoxifen, in women with breast cancer is still debated. We evaluated the association between AI and CV outcomes in a large population-based cohort of breast cancer women. Methods: By using healthcare utilization databases of Lombardy (Italy), we identified women ≥50 years, with new diagnosis of breast cancer between 2009 and 2015, who started adjuvant therapy with either AI or tamoxifen. We estimated the association between exposure to AI and CV outcomes (including myocardial infarction, ischemic stroke, heart failure or any CV event) by a Cox proportional hazard model with inverse probability of treatment and censoring weighting. Results: The study cohort included 26,009 women starting treatment with AI and 7937 with tamoxifen. Over a median follow-up of 5.8 years, a positive association was found between AI and heart failure (Hazard Ratio = 1.20, 95% CI: 1.02 to 1.42) and any CV event (1.14, 1.00 to 1.29). The CV risk increased in women with previous CV risk factors, including hypertension, diabetes and dyslipidemia. Conclusions: Adjuvant therapy with AI in breast cancer women aged more than 50 years is associated with increased risk of heart failure and combined CV events.

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Endogenous hormones and risk of invasive breast cancer in pre- and post-menopausal women: findings from the UK Biobank

British Journal of Cancer ◽

10.1038/s41416-021-01392-z ◽

2021 ◽

Author(s):

Sandar Tin Tin ◽

Gillian K. Reeves ◽

Timothy J. Key

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Invasive Breast Cancer ◽

Cox Regression ◽

Menopausal Status ◽

Endogenous Hormones ◽

Uk Biobank ◽

Menopausal Women ◽

Post Menopausal

Abstract Background Some endogenous hormones have been associated with breast cancer risk, but the nature of these relationships is not fully understood. Methods UK Biobank was used. Hormone concentrations were measured in serum collected in 2006–2010, and in a repeat subsample (N ~ 5000) in 2012–13. Incident cancers were identified through data linkage. Cox regression models were used, and hazard ratios (HRs) corrected for regression dilution bias. Results Among 30,565 pre-menopausal and 133,294 post-menopausal women, 527 and 2,997, respectively, were diagnosed with invasive breast cancer during a median follow-up of 7.1 years. Cancer risk was positively associated with testosterone in post-menopausal women (HR per 0.5 nmol/L increment: 1.18; 95% CI: 1.14, 1.23) but not in pre-menopausal women (pheterogeneity = 0.03), and with IGF-1 (insulin-like growth factor-1) (HR per 5 nmol/L increment: 1.18; 1.02, 1.35 (pre-menopausal) and 1.07; 1.01, 1.12 (post-menopausal); pheterogeneity = 0.2), and inversely associated with SHBG (sex hormone-binding globulin) (HR per 30 nmol/L increment: 0.96; 0.79, 1.15 (pre-menopausal) and 0.89; 0.84, 0.94 (post-menopausal); pheterogeneity = 0.4). Oestradiol, assessed only in pre-menopausal women, was not associated with risk, but there were study limitations for this hormone. Conclusions This study confirms associations of testosterone, IGF-1 and SHBG with breast cancer risk, with heterogeneity by menopausal status for testosterone.

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Reproductive risk factors and breast cancer: a case control study from rural India

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v14i3.21865 ◽

2015 ◽

Vol 14 (3) ◽

pp. 258-264 ◽

Cited By ~ 3

Author(s):

Vaishali R Mohite ◽

Asha K Pratinidhi ◽

Rajsinh Vishwasrao Mohite

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Breast Feeding ◽

Menopausal Status ◽

Hormonal Contraceptives ◽

Reproductive Risk ◽

History Of ◽

Reproductive Risk Factors ◽

Post Menopausal ◽

Strength Of Association

Background: Breast cancer is the most common type of cancer in women and is influenced by reproductive factors perceived by women worldwide.Aims: To identify the reproductive risk factors of breast cancer in newly diagnosed cases and to find out the strength of association of the risk factors with the breast cancer. Material and Methods: A hospital based case-control study was conducted in Satara district, India during year 2009 to 2011 among newly diagnosed cases of breast cancer and matched controls. A total of 434 participants including 217 cases and 217 controls were enrolled by purposive sampling technique from selected hospitals of study area. The information was collected by employing pre-tested questionnaire by utilizing interview method. Statistical Analysis used: Descriptive statistics, Odds ratio and Chi-square test was used to find out strength of association and statistical significant difference. Results: Highest proportion [31.80%] breast cancer cases was in age group 40-49 years with lowest age of 25 years at diagnosis of the disease. A very high proportion of both cases [88.02%] and controls [67.28%] were Hindu by religion and were from rural residence. Maximum proportion of breast cancer cases were housewives [63.59%], literate [71.42%] and from upper economic class [56.68%]. The proportions of cases were higher as compared to the controls with respect to risk factors like unmarried status, nulliparity, history of abortion, post menopausal status, absence of breast feeding and the history of exposure to hormonal contraceptives. The risk of getting breast cancer as indicated by Odds ratio was 8 times higher in unmarried women, 2.8 times in nulliparous women, 2.4 times with post menopausal status, 10.4 times with absence of breast feeding, 1.5 times with exposure to hormonal contraceptives and 4.5 times with history of ovarian disease respectively. Conclusion: The reproductive risk factors such as unmarried status of women, nulliparity, menopause, absence of breast feeding, history of ovarian disease and use of contraceptives were strongly associated with breast cancer.Bangladesh Journal of Medical Science Vol.14(3) 2015 p.258-264

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Influence of preoperative MRI on the surgical management of patients with operable breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.613 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 613-613 ◽

Cited By ~ 1

Author(s):

M. W. Braun ◽

M. Pölcher ◽

S. Schrading ◽

O. Zivanovic ◽

T. Kowalski ◽

...

Keyword(s):

Breast Cancer ◽

Surgical Management ◽

Clinical Management ◽

Menopausal Status ◽

Breast Mri ◽

Breast Ultrasound ◽

Operable Breast Cancer ◽

Tumor Characteristics ◽

Mri Findings ◽

The Impact

613 Background: To evaluate the impact of preoperative magnetic resonance imaging (MRI) of the breast on the clinical management of patients with operable breast cancer (BC). Methods: Retrospective analysis of 160 patients with operable breast cancer (stages Tis, through T4), who were treated from 2002 through 2004. All patients underwent a full mammographic assessment, high frequency breast ultrasound, and breast MRI. The impact of preoperative MRI was evaluated for each patient with regard to changes in the therapeutic procedure. Patient and tumor characteristics were analysed to identify possible patient subgroups that predominantly benefit from preoperative MRI. Results: Preoperative MRI affected the clinical management in 44 of 160 patients (27.5%). In 30 cases (18.75%) additional in-situ or invasive cancers or a more widespread tumor extent were diagnosed correctly which went undetected by clinical palpation, mammography, and breast ultrasound. In 14 cases (8.75%) additional, surgical procedures were performed based on suspicious MRI findings with benign pathology. Age, menopausal status, breast density, tumor characteristics (type, tumor size, grading), ER-, PR- and HER2- receptor features did not significantly differ between patients in which breast MRI affected the clinical management and patients that experienced no additional information from MRI. Conclusions: Preoperative breast MRI changes surgical management in a considerable amount of patients with operable breast cancer. MRI detects additional invasive carcinoma and proves to be a meaningful supplement to the conventional work-up in the clinical management of breast cancer. This benefit is independent from patients and tumor characteristics. No significant financial relationships to disclose.

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10-year update of E2197: Phase III doxorubicin/docetaxel (AT) versus doxorubicin/cyclophosphamide (AC) adjuvant treatment of LN+ and high-risk LN- breast cancer and the comparison of the prognostic utility of the 21-gene recurrence score (RS) with clinicopathologic features.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.1021 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 1021-1021 ◽

Cited By ~ 4

Author(s):

Joseph A. Sparano ◽

Anne O'Neill ◽

Robert James Gray ◽

Edith A. Perez ◽

Lawrence N. Shulman ◽

...

Keyword(s):

Breast Cancer ◽

Menopausal Status ◽

Disease Free Survival ◽

Recurrence Score ◽

Phase Iii ◽

Clinicopathologic Characteristics ◽

Accurate Predictor ◽

Gene Assay ◽

Node Positive Disease

1021 Background: At 5 years, AT did not improve disease free survival or overall survival and RS was a more accurate predictor of relapse than standard clinicopathologic characteristics for patients with hormone receptor (HR) positive tumors. Methods: A Phase III Intergroup trial tested adjuvant AT vs. AC. Women with 1-3 N + or N - and T-size > 1cm were randomized to 4 cycles of AT (60 mg/m2/60 mg/ m2) or AC (60 mg/m2/600 mg/m2) q 3 wk x 4. Patients(pts) with ER + and/ or PR + tumors received tam for 5 yrs. Pts were stratified by nodal, HR (ER+ PR+, ER+PR-, ER-PR+, ER-PR-, ER/PR unk) and menopausal status. The primary endpoint was DFS. A sample of 465 pts with HR + breast cancer with 0 to 3 positive axillary nodes who did (N =116) or did not have a recurrence had tumor tissue evaluated using the 21- gene assay. Grade and HR expression were evaluated locally and centrally. Results: 2952 pts were randomized between 7/30/98 and 1/21/00. 2883 were eligible and analyzable. Arms were balanced for age, HR, menopause, nodes, surgery, grade and T-size: median age 51; 64% ER +; 65% LN-; grade: 10% low, 38% int., 46% high; and median T-size - 2.0 cm. At a median follow-up of 11.5 years the DFS/OS results are shown in the table below. RS was a highly significant predictor of recurrence including node negative and node positive disease (P < .0001) and predicted recurrence more accurately than clinical variables. Conclusions: At 11.5 yrs. median follow-up, there remains no difference in DFS or OS, although there continue to be fewer events in the AT arm in the prespecified ER/PR negative subgroup. At 10 years, the RS continues to be a more accurate predictor of relapse than standard clinical features. [Table: see text]

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Patient-reported cognitive impairments among women with breast cancer randomly assigned to hormonal therapy (HT) alone versus chemotherapy followed by hormonal therapy (C+HT): Results from the Trial Assigning Individualized Options for Treatment (TAILORx).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9020 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9020-9020

Author(s):

Lynne I. Wagner ◽

Robert James Gray ◽

George W. Sledge ◽

Timothy Joseph Whelan ◽

Daniel F. Hayes ◽

...

Keyword(s):

Breast Cancer ◽

Hormonal Therapy ◽

Cognitive Impairments ◽

Menopausal Status ◽

Recurrence Score ◽

Well Being ◽

Control Group ◽

Breast Cancer Patients ◽

Change Scores ◽

Patient Reported

9020 Background: Cognitive impairment is a complication of chemotherapy. Perceived cognitive impairments (PCI) were prospectively assessed among TAILORx participants randomized to HT alone versus chemotherapy followed by HT (C+HT). Methods: TAILORx participants with an OncoType DX Recurrence Score 11-25 were randomly assigned to HT or C+HT. PCI, fatigue, endocrine symptoms and health-related quality of life (HRQL) were assessed at baseline, 3, 6, 12, 24, and 36 months, using the Functional Assessment of Cancer Therapy (FACT) in 455 patients enrolled after 1/15/10. PCI change scores > 4.5 from baseline were defined a priori as clinically meaningful. Linear regression (LR) was used to model PCI scores on baseline PCI, treatment and other factors. Results: PCI scores were significantly worse at 3, 6, and 12 months compared to baseline for both groups (Table). The decline was greater for C+HT than HT at 3 months, but scores were similar at 12 months. Tests of an interaction between menopausal status and treatment were non-significant. PCI correlated with fatigue (r = 0.57-0.64) but not FACT Emotional well-being (EWB; r = 0.28-0.38); controlling for EWB did not account for differences in PCI change scores between treatment arms. Conclusions: Our study is the first to examine PCI among breast cancer patients randomized to receive C+HT vs. HT alone. C+HT was associated with greater declines in PCI at 3 months, but at 12 months PCI was similar in the C+HT and HT groups. PCI was associated with fatigue but not EWB. Pre- and post-menopausal groups demonstrated the same pattern of change. Since this study did not include a control group of patients not treated with HT, further study is required to determine if and to what extent HT contributes to PCI. [Table: see text]

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The Association between Treatment for Metabolic Disorders and Breast Cancer Characteristics

International Journal of Endocrinology ◽

10.1155/2016/4658469 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Hadar Goldvaser ◽

Shulamith Rizel ◽

Daniel Hendler ◽

Victoria Neiman ◽

Daniel Shepshelovich ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Disorders ◽

Growth Factor Receptor ◽

Recurrence Score ◽

Retrospective Chart Review ◽

Breast Cancer Diagnosis ◽

Study Cohort ◽

Er Positive ◽

Study Population ◽

Statin Usage

Purpose. To evaluate the associations between metformin, insulin, statins, and levothyroxine and breast cancer characteristics and outcome.Methods. Retrospective chart review of patients treated in our institute for early estrogen receptor (ER) positive, human epidermal growth factor receptor 2 negative breast cancer, whose tumors were sent to Oncotype DX (ODX) analysis. Patients were grouped according to medications usage during the time of breast cancer diagnosis. Each group was compared to the rest of the study population.Results. The study cohort included 671 patients. Sixty (9.1%) patients were treated with metformin, 9 (1.4%) with insulin, 208 (31.7%) with statins, and 62 (9.4%) with levothyroxine. Patients treated with metformin had more intense ER stain (p=0.032) and a lower ODX recurrence score (RS) (p=0.035). Diagnosis of diabetes mellitus was also associated with lower ODX RS (p=0.014). Insulin usage was associated with a higher rate of angiolymphatic invasion (p=0.041), but lower Ki67% (p=0.017). Levothyroxine usage was associated with different histological subtype distribution (p=0.02). Extended levothyroxine usage was associated with lower ODX RS (p=0.005). Statin usage had no impact on tumor characteristics. Outcome was comparable in the studied subgroups.Conclusions. Common medications for metabolic disorders might be associated with breast cancer characteristics.

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The Relationship of 25-Hydroxyvitamin D Plasma Levels with Breast Cancer Stadium Assessed from Menopause Status

Britain International of Exact Sciences (BIoEx) Journal ◽

10.33258/bioex.v3i1.383 ◽

2021 ◽

Vol 3 (1) ◽

pp. 65-72

Author(s):

Ika Waraztuty ◽

Astrid Siska Pratiwi ◽

Melya Susanti ◽

Ira Astuti ◽

Zakirullah

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Plasma Levels ◽

Menopausal Status ◽

Observational Research ◽

Cancer Stage ◽

Hydroxyvitamin D ◽

25 Hydroxyvitamin D ◽

Post Menopausal ◽

The Relationship

Breast cancer is a type of cancer with high incidence and mortality especially in developing countries. Vitamin D regulates the expression a number of genes involved in the development of cancer cells. The aim of this study is to analyze the relationship between 25-hydroxyvitamin D (25 (OH) D) plasma level with breast cancer stage based on menopausal status. This is an observational research method with cross sectional design. Research subjects were 53 newly diagnosed breast cancer patients and had not received chemotherapy. Menopausal status and stage data were obtained from interviews and medical record data. Levels of 25-hydroxyvitamin D plasma were measured (ELISA) method. The results obtained Stage II, III and IV each have an average level of vitamin D of 28,56 ng/ml (95% CI; 23,61 – 33,52 ng/ml), 28,18 ng/ml (95% CI: 24,49 – 31,87 ng/ml) and 27,86 ng/ml (95% CI: 22,68 – 33,04 ng/ml).The average plasma concentration of 25 (OH) D in pre-menopausal patients is 28,54 ng/ml and average plasma 25 (OH) D levels in post-menopausal patients is 27,79 ng/ml. There was no significant relationship between plasma levels of 25 (OH) D and breast cancer stage in both pre-menopausal and post-menopausal patients.

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673Is weight more informative than body mass index for breast cancer risk

International Journal of Epidemiology ◽

10.1093/ije/dyab168.734 ◽

2021 ◽

Vol 50 (Supplement_1) ◽

Author(s):

Zhoufeng Ye ◽

Gillian Dite ◽

John Hopper

Keyword(s):

Breast Cancer ◽

Body Mass Index ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Body Mass ◽

Cox Regression ◽

Menopausal Status ◽

Familial Risk ◽

Study Cohort ◽

Breast Cancers

Abstract Background Our previous work on body mass index (BMI) and breast cancer risk found that the association depended on menopausal status but not on familial risk (Hopper, JL., et al, 2018). We now consider whether weight is a more informative risk factor for breast cancer than BMI. Methods We used data from the Prospective Family Study Cohort, a consortium of international prospective cohorts that are enriched for familial risk of breast cancer and include 16,035 unaffected women from 6701 families. Participants were followed for up to 20 years (mean 10.5 years) and there were 896 incident breast cancers with a mean age at diagnosis of 55.7 years. Cox regression was used to model risk associations as a function of age, menopausal status and underlying familial risk. We calculated robust confidence intervals by clustering by family. Model comparisons were made using the Bayesian Information Criterion (BIC). Results In repeating the best-fitting model from our original analyses, but using weight instead of BMI, we found that the log likelihood for the model using weight was 1.92 units greater than for the model using BMI (difference in BIC = 3.84). Therefore, the data are almost 50 times more likely under the model using weight. Conclusions The study found positive evidence that weight gives more information on risk than does BMI. Key messages Analysing breast cancer risk in terms of weight, rather than only BMI, might give greater insight and results that are easier to convey to the public.

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