Use Of Hormone Replacement Therapy Research Articles

Abstract PO3-27-09: A Multidisciplinary Telehealth Approach to Breast Cancer Prevention in a Veteran Population

Abstract INTRODUCTION An estimated 13% of women will be diagnosed with breast cancer at some point in their lifetime. There are non-modifiable and modifiable risk factors including family history, genetics, obesity, and estrogen exposure. Interventions that reduce breast cancer risk and/or mortality include screening, chemoprevention, and lifestyle modification. A recent national survey shows that there are significant gaps in providing breast cancer prevention care for female Veterans. We describe the creation of a multi-disciplinary telehealth clinic aimed at reducing breast cancer risk in a high-risk female Veteran population. METHODS The breast cancer prevention clinic (BCPC) team consists of a medical oncologist, geneticist, genetic counselor, dietician, psychologist, and nurse navigator. High risk women are identified through a combination of screening questionnaires at annual mammography and genetics or primary care provider (PCP) evaluation, then referred to the clinic. Criteria for referral include age >=35, Gail 5 year risk >= 1.7%, Tyrer-Cuzick 10 year risk >= 5%, or history of thoracic radiation. At the BCPC telehealth visit, the medical oncologist makes individualized recommendations about chemoprevention by discussing the risks and possible complications of therapy. Use of screening magnetic resonance imaging (MRI) is also recommended to women with lifetime Tyrer-Cuzick score > 20%. Within the same visit, patients meet with a dietician to discuss nutrition modification, and a psychologist to address psychosocial barriers to lifestyle change. Those who start chemoprevention attend a 3 month follow-up with a nurse navigator to discuss tolerability and side effects. Subsequently, the patient’s PCP becomes responsible for management of chemoprevention and annual breast MRI. RESULTS Between January and December 2022, 33 patients were seen in BCPC. Patients had an average age of 52 years (range 42-70), Gail 5-year score of 2.53%, Tyrer-Cuzick 10-year score of 6.65%, and Tyrer-Cuzick lifetime score of 21.5%. Thirteen patients (39.4%) started chemoprevention, the majority of which were selective estrogen receptor modulators (SERM). Nine reported starting the medication at the 3 month follow-up appointment. The most reported side effect was hot flashes in 67%, although only the majority had mild symptoms. Three reported weight gain and one reported vaginal dryness. None reported worsening arthralgia or fatigue. Despite the low incidence of severe symptoms, only 3 continued to fill the medication at the time of chart review in August 2023. Twenty (60.6%) patients did not initiate chemoprevention. Four (20%) did not qualify due to cardiovascular or thrombotic risk factors, and three (15%) did not qualify due to concurrent use of hormone replacement therapy. Two (10%) elected not to start chemoprevention because they were planning for risk reducing mastectomies. Eleven (55%) did not initiate chemoprevention due to patient preferences and concern for side effects. Twenty-eight patients were recommended to obtain breast MRI in addition to mammogram for yearly screening. At time of chart review, 15 had at least one screening breast MRI ordered by PCP after BCPC visit, with 10 MRIs performed. CONCLUSIONS The unique interdisciplinary model of our breast cancer prevention clinic allows for a comprehensive and personalized evaluation for high-risk female Veterans on interventions to reduce their breast cancer risk. However, the current model does not ensure long-term compliance with these interventions. Studies have shown that more frequent/short-term follow up may improve compliance with endocrine therapies. Future directions include clinic expansion and providing additional follow-up with the multidisciplinary team to promote continued adherence to BCPC interventions. Citation Format: Hanqing Shang, Sarah Ansari, Shweta Dhar, Mahdieh Irranejadparizi, Stacey Edwards, Jessica Honkomp, Meagan Siehr, Bethany Aiena, Mary Nikityn, Diana Bearden, Deleene Menefee, Sita Bushan. A Multidisciplinary Telehealth Approach to Breast Cancer Prevention in a Veteran Population [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-27-09.

Abstract PO4-17-03: Neoadjuvant chemotherapy in invasive lobular carcinoma of the breast: A retrospective study on survival outcomes

Abstract Background: Neoadjuvant chemotherapy (NAC) is a well-established component of breast cancer management. Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are often treated similarly, but many studies are demonstrating a major difference in treatment responses according to the histopathological type of cancer. Aim: To evaluate the overall survival of patients with ILC after NAC compared with adjuvant chemotherapy. Methods: This retrospective cohort study included patients treated for breast ILC between 1998 and 2016 at the Center for Breast Diseases of de CHU de Québec – Université Laval, a tertiary breast cancer center. The primary outcomes were the overall survival (OS) and the recurrence-free survival (RFS) of ILC patients receiving NAC compared with patients who received only adjuvant chemotherapy. The follow-up was censored at the last hospital contact. The secondary outcomes were the locoregional recurrence, pathological complete response (pCR), and pCR impact on survival. Results: During the study period, 265 women were treated for ILC, of which 72 had NAC, and 193 had adjuvant therapy. No significant differences were observed regarding the patient’s characteristics (age, BMI, smoking, menopausal status, and use of hormonal replacement therapy). A T4 disease was found in 29.2% of the NAC group (vs. 0 in the adjuvant group), but the N2-3 rate was lower in the NAC group (5.6% vs. 22.3%, P=0.011). More patients in the NAC group underwent mastectomy (65.3% vs. 29.5%, P< 0.0001) and axillary dissection (80.6% vs. 50.8%, P< 0.0001). Three (4.2%) patients in the NAC group achieved a pCR. The rates of radiotherapy (P=0.851) and hormonal therapy (P=0.694) were similar between the two groups. The mean follow-up was 8 years. After adjustment for age, T, N, surgery type, radiotherapy, and hormonal therapy, the NAC group showed significantly lower 10-year OS (56.2% vs. 80.7%, P< 0.0001) and RFS (51.8% vs. 72.7%, P=0.0004) compared with the adjuvant group. There were no differences in the 10-year local recurrence rate (90.6% vs. 93.5%, P=0.11). In a Cox regression analysis of RFS considering the previously mentioned covariables, more events in the NAC group (OR=2.52, 95%CI: 1.39-4.58, P=0.002) and patients with N2-N3 (OR=3.68, 95%IC: 2.00-6.80, P< 0.01). Conclusion: Despite the general belief that ILC and IDC should be treated similarly, this study strongly suggests that ILC seems to have a poorer response to NAC. Patients diagnosed with ILC might benefit from a more aggressive surgical approach followed by adjuvant chemotherapy, no matter the severity of the disease. Additional long-term prospective comparative studies are needed to support this statement and improve the management of these patients. Citation Format: Virginie Gauthier, Anne-Julie Simard, Christine Desbiens, Brigitte Poirier, Julie Lemieux, Dominique Boudreau, Dominique Leblanc, Claudya Morin, Jean-Charles Hogue, Éric Poirier. Neoadjuvant chemotherapy in invasive lobular carcinoma of the breast: A retrospective study on survival outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-03.

Recurrent postmenopausal bleeding: Pathological findings andpredictive factors. A multicenter, prospective, observational study.

Recurrent postmenopausal bleeding (PMB) occurs in 6%-25% of postmenopausal women who have experienced a previous episode of PMB. The question of whether recurrent PMB leads to a higher risk of endometrial cancer (EC) in comparison to a single episode of PMB is, however, controversial. Furthermore, little is known about predictive factors for recurrent PMB. A multicenter prospective cohort study was conducted over a 5-year period in four hospitals in the Netherlands. Women with PMB undergoing endometrial sampling and aged 40 years and older were included. Occurrence of recurrent PMB was retrospectively determined. Primary outcomes included (1) the incidence of recurrent PMB and (2) differences in pathological findings between patients with a single episode versus recurrent PMB. Secondary outcomes included (1) the association between diagnosis of benign polyps at first PMB and pathological findings at recurrent PMB and (2) factors predictive for recurrent PMB. A total of 437 women with PMB were included, of whom 360 were at risk of recurrent PMB. With a median follow-up of 61 months (IQR (Interquartile range)44-73), 26.4% experienced recurrent PMB. Patients with recurrent PMB were more often diagnosed with benign polyps (34.7% vs. 25.1%, p-value 0.015) and less frequently with a malignancy (5.3% vs. 17.8%, p-value 0.015), compared to patients with a single episode of PMB. Benign polyps at initial PMB were not associated with a (pre)malignancy at recurrence (OR 4.16, 95% CI 0.75-23.03). Predictive factors for recurrent PMB included use of hormone replacement therapy (HRT) (OR 3.32, 95% CI 1.64-6.72), and benign polyps at initial PMB (OR 1.80, 95% CI 1.07-3.04). Recurrent PMB is common in women with a previous episode of PMB. Compared to patients with a single episode of PMB, patients with recurrent PMB and benign histological outcomes at accurate workup during their first episode were less often diagnosed with malignancies and more frequently with benign polyps. Benign polyps at first PMB are predictive for recurrent PMB, but not for a higher risk of (pre)malignancy.

P126 Use of oral contraceptives in females with rheumatoid arthritis is not associated with an increased risk of venous thromboembolism: United Kingdom-population based study

Abstract Background/Aims While the use of oral contraceptives in females with immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) is acknowledged as a risk factor for venous thromboembolism (VTE), the interaction between oral contraceptive use and RA is poorly understood. In a large population-based study, we aimed to estimate RA-attributable VTE risk in females using oestrogen contraceptives and/or on hormone replacement therapy (HRT). Methods Females registered with a general practice from January 1999 to December 2018 were identified from the Royal College of General Practitioners Research (RCGP) and Surveillance Centre (RSC) database. Female RA patients and VTE outcome (composite of pulmonary embolism and deep vein thrombosis) were determined using previously-validated algorithms. Female unaffected controls (UCs) were matched 4:1 with RA patients by current age (per year), calendar time, and years since practice registration using nearest neighbour matching, with replacement. Absolute VTE rates over 20 years were compared in RA patients versus matched UCs, overall and in two different subgroups defined by the use of oestrogen contraceptives or HRT. Relative VTE risk over the same period was estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (BMI [body-mass index], smoking status, alcohol use, evidence of reduced mobility, thrombophilia, fracture of the lower limb and family history of VTE). Results A total of 82,082 female adults were included in this study, of whom 16,634 were RA patients and 65,448 were UCs. Average study follow-up was 8.3 years (standard deviation [SD]=6.2 years). Female RA patients (mean age 58.3, SD 16.5; mean BMI 27.0, SD 5.9) were similar to matched UCs in their clinical characteristics. Compared to UCs, females with RA were less likely to receive oral contraceptives (RA n = 545 [3.3%], UCs n = 2,542 [3.9], p < 0.001) but more likely to receive HRT (RA n = 752 [4.5%], UCs n = 2,460 [3.8], p < 0.001). Unadjusted VTE events rates were consistently higher in females with RA compared to UCs (430.2 per 100,000 person-years [py], 95% confidence interval [CI]: 396.1, 466.3; UC: 260.5 per 100,000 py, 95%CI: 247.1, 274.4) and in those receiving and not receiving oral contraceptives and HRT. Overall, relative risk of VTE was 52% higher in females with RA compared UCs (adjusted hazard ratio [aHR]= 1.52, 95%CI: 1.36, 1.71, p < 0.001). Compared to UCs, relative risk increases were not statistically significant for females with RA receiving oral contraceptives (aHR 1.43; 95%CI 0.60, 3.63, p = 0.46) and HRT (aHR 2.32; 95%CI 0.92, 5.85, p = 0.08). Conclusion UK data suggest that all women with RA are at a similarly increased risk of VTE irrespective of the use of oestrogen contraceptives or HRT, although larger studies are needed to confirm this finding. It is therefore advisable to conduct routine VTE risk factor assessments for all females with RA. Disclosure J. Galloway: Honoraria; JG has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UC. V. Basey: Corporate appointments; Pfizer employee. A. Barkaway: Corporate appointments; Pfizer employee. S. de Lusignan: Grants/research support; SdeL has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, Takeda and Moderna. Other; Director of the RCGP RSC. M.H. Buch: Consultancies; M.H.B. has provided expert advice and received/paid to employer consultant fees from AbbVie, Eli Lilly, EMD serono, Gilead, Pfizer and Sanofi. Grants/research support; .H.B. has received research grants paid to her employer from Gilead Ltd, Pfizer Ltd, Roche and UCB.

Hormone replacement therapy and the incidence and prevalence of breast cancer: an integrative review

The objective of this study was to carry out an integrative review an integrative review to analyze the incidence and prevalence of breast cancer after hormone replacement therapy. This integrative review followed several steps, including identifying the topic, structuring the research question using the PICO strategy, defining inclusion criteria, selecting articles, evaluating and analyzing selected studies, interpreting the results and presenting the review. The use of hormone replacement therapy (HRT) is linked to a significantly increased risk of breast cancer, especially with combination therapy. The risk increases with time of use and persists after discontinuation. Although some studies have found a significant risk, estrogen-only therapy carries a lower risk, particularly for long-term use. Hormone replacement therapy, especially the combined formulation of estrogen and progestogen, is associated with a significant increase in the risk of breast cancer, persisting after discontinuation. The estrogen-only formulation has a lower risk. The duration of HRT and body mass index (BMI) also influence the risk.

Hormone replacement therapy in women with iatrogenic premature ovarian insufficiency after radiotherapy for cervical cancer: A retrospective cohort and survey study

ObjectivesThis study assessed the uptake of hormone replacement therapy (HRT) in cervical cancer patients with iatrogenic menopause. Survival in relation to HRT use was assessed via a retrospective chart study, and the severity of menopausal symptoms, motivations and barriers to starting HRT were examined via questionnaires. Study designIn total, 293 women under the age of 51 and treated with radiotherapy for cervical cancer between 2010 and 2020 were identified. Medical records were searched for information on HRT use. If still living, women were sent digital questionnaires addressing menopausal symptoms, quality of life (QoL) and potential barriers and motivations concerning HRT use. Univariable data were analysed using Mann-Whitney U, chi-square, and Fisher's exact test, while logistical regression was used to analyse relationships between certain variables and use of HRT and survival. ResultsOverall HRT uptake was 78.1 %, which was related to age and Charlson Comorbidity Index, but independent of the duration of radiotherapy or FIGO stage. Overall survival was higher for HRT users (χ2(1) = 4.3, p = 0.038). Questionnaires were sent to 193 patients and 100 completed it (response rate 51.8 %). Main reasons for HRT use were relief of hot flushes and improvement in QoL. For women below age 51, QoL was indeed higher for current HRT users than for non-HRT users (EQ-index 0.8 vs. 0.7, p = 0.008). ConclusionsHRT prescription rate was inversely correlated with age. Survival was not negatively affected by HRT use. It is important to stress the benefits of HRT and address women's fears regarding its use.

Assessing Agreement to the Use of Hormone Replacement Therapy for Breast Cancer Patients Experiencing Menopausal Symptoms

Assessing Agreement to the Use of Hormone Replacement Therapy for Breast Cancer Patients Experiencing Menopausal Symptoms

Exogenous Estrogen in the Development of Head and Neck Cancer

Sex differences in head and neck cancer (HNC) incidence suggest a potential contribution of sex hormones. To assess the role of exogenous estrogen exposure in the development of HNC in female patients. This large multicenter cohort study using clinical records from the TriNetX real-world database included 20 years of data (through May 31, 2023) from 87 health care organizations. The TriNetX database was searched for medical records for female patients with and without exogenous estrogen exposure according to their chronological age. Cohort 1 included 731 366 female patients aged 18 to 45 years old with regular oral contraceptive (OC) intake and cohort 2 included 3 886 568 patients in the same age group who did not use OC. Cohort 3 comprised 135 875 female patients at least 50 years old receiving hormone replacement therapy (HRT), whereas cohort 4 included 5 875 270 patients at least 50 years old without HRT. Propensity score matching was performed for the confounders age, alcohol dependence, and nicotine dependence. Data analyses were performed in May 2023. Diagnosis of HNC (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision: C00-C14), and after propensity score matching (1:1 nearest-neighbor greedy matching), a risk analysis to investigate risk differences and risk ratios (RRs) with a 95% CI. Among the 718 101 female patients in each of cohorts 1 and 2 (mean [SD] age at diagnosis, 25.9 [6.7] years), those with OC intake had a higher risk of an HNC diagnosis (RR, 1.47; 95% CI, 1.21-1.78) than those without OC use. Among the 131 835 female patients in each of cohorts 3 and 4 (mean [SD] age, 67.9 [12.0] years), those with postmenopausal HRT intake had a lower risk of an HNC diagnosis (RR, 0.77; 95% CI, 0.64-0.92) than those without HRT use. The findings of this cohort study illustrate a positive association between OC and a negative association between HRT and the development of HNC in female patients. Given the limitations of the TriNetX database, future research should include detailed information on the intake of OC and HRT and reproductive health information (eg, age at menarche/menopause, number of pregnancies) to more accurately define the strength and direction of the possible association between exogeneous estrogen exposure and the development of HNC in female patients.

Abstract P243: Association Between a Brain Care Score and Risk of Cerebrovascular Events in American Women

Background: The McCance Brain Care Score (MBCS) is a novel tool derived through a modified Delphi process to motivate lifestyle changes to reduce the risk of cerebrovascular events (CVE) based on prior studies and expert knowledge. However, few studies to date have determined the association between the MBCS and incident CVE. Studying this potential association is particularly important given the higher risk of stroke among women and the potential for unique risk profiles given physiologic and pharmacologic hormonal changes across the lifespan. Methods: The study population was participants in the Women’s Health study (WHS) who had available risk factor information needed to calculate the modified MBCS 5 years after enrollment and no prior history of CVE. The WHS-adaptation of the MBCS is illustrated in Figure 1; higher scores suggest better brain health. Participants were followed from MBCS assessment until first CVE (Stroke or Transient Ischemic Attack), end of study, loss to follow-up, or death, whichever occurred first. CVE were confirmed by medical record review. Cox proportional hazards models were used to examine the association between the MBCS, modeled as a continuous variable, and incident CVE adjusted for potential confounders. Results: In total, 22,965 women were eligible with a median age of 58.0 (Interquartile Range 54.0-63.9) and median MBCS of 15 (14-17). There were 1,364 (5.9%) incident CVE events during a median follow-up of 22.5 (16.8-23.6) years. A one-point higher baseline MBCS was associated with 11% decreased risk of incident CVE after adjusting for age, postmenopausal status, and use of hormonal replacement therapy (HR=0.89; 95%CI=0.87-0.91). This association remained significant after adjusting for comorbidities, race, educational attainment, and income (HR=0.90; 95%CI=0.88-0.93). Conclusion: Higher baseline MBCS was associated with a decreased risk of incident CVE among women. Future studies are needed to understand how longitudinal changes in the MBCS impact risk of CVE.

Associations between breast cancer risk factors and mammographic breast density in a large cross-section of Korean women.

We investigated the association between established risk factors for breast cancer and mammographic breast density in Korean women. This large cross-sectional study included 8 460 928 women aged >40 years, who were screened for breast cancer between 2009 and 2018. Breast density was assessed using the Breast Imaging Reporting and Data System. This study used multiple logistic regression analyses of age, BMI, age at menarche, menopausal status, menopausal age, parity, breastfeeding status, oral contraceptive use, family history of breast cancer, physical activity, smoking, drinking and hormone replacement therapy use to investigate their associations with mammographic breast density. Analyses were performed using SAS software. Of 8 460 928 women, 4 139 869 (48.9%) had nondense breasts and 4 321 059 (51.1%) had dense breasts. Factors associated with dense breasts were: earlier age at menarche [<15 vs. ≥15; adjusted odds ratio (aOR), 1.18; 95% confidence interval (CI), 1.17-1.18], premenopausal status (aOR, 2.01; 95% CI, 2.00-2.02), later age at menopause (≥52 vs. <52; aOR, 1.23; 95% CI, 1.22-1.23), nulliparity (aOR, 1.64; 95% CI, 1.63-1.65), never breastfed (aOR, 1.23; 95% CI, 1.23-1.24) and use of hormone replacement therapy (aOR, 1.29; 95% CI, 1.28-1.29). Women with a higher BMI and the use of oral contraceptives were more likely to have nondense breasts. Lower BMI, reproductive health and behavioral factors were associated with dense breasts in Korean women. Additional research should investigate the relationship between mammographic breast density, breast cancer risk factors and breast cancer risk.

Hormone Replacement Therapy and Risks of Various Cancers in Postmenopausal Women with De Novo or a History of Endometriosis.

This study examined the impact of hormone replacement therapy (HRT) on the occurrence of various cancers in postmenopausal women with de novo or a history of endometriosis. In the datasets for ten cancers (cervical, uterine, ovarian, breast, colon, gastric, liver, lung, pancreatic, and thyroid), women who received HRT (the HRT group) and those who did not (the control group) were selected by a 1:1 matching with those who met the study criteria. In the dataset for each cancer, the incidence of each cancer was very low (0.2% to 1.5% in the HRT group and 0.2% to 1.3% in the control group). The duration of HRT was 1.3 ± 2.1 years. After adjusting for co-variables, HRT was a significant risk factor for uterine cancer (p < 0.05). However, the risk of liver cancer decreased significantly with duration of HRT (p < 0.05). Moreover, combined estrogen and progesterone decreased the risks of liver and thyroid cancers significantly (p < 0.05), and estrogen alone decreased the risks of breast and lung cancers significantly (p < 0.05). Tibolone was not associated with the risk of any of the cancers assessed. These results can help guide the use of HRT in women with de novo or a history of endometriosis.

Could sex-specific subtypes of hand osteoarthritis exist? A retrospective study in women presenting to secondary care.

Hand osteoarthritis is more common in women, and its risk increases around the time of the menopause. We set out to describe the timing between menopause and the onset of symptomatic hand osteoarthritis (OA), and associations with the use of hormone replacement therapy (HRT) or its discontinuation, describing any identifiable subgroups of women. Retrospective healthcare-records study of sequential women referred to a specialist hand OA clinic, 2007-2015. Confirmation of hand OA diagnosis was by clinican, by accepted criteria. Demographics and clinical variables were from healthcare-records, recorded by standardised proforma. Outcomes of interest were reported age of onset of hand symptoms, reported age at final menstrual period (FMP), time from FMP to reported onset of hand symptoms and time from cessation of HRT to reported onset of hand symptoms. Exposure categories for systemic HRT use were never users, current users, previous users. Analysis of Variance compared groups; linear regression analysed associations of exposure with outcome. 82/92(89%) of eligible women were post-menopausal, mean age at FMP 49.9 years (SD5.4). In these post-menopausal women, median time from FMP to hand symptom onset was 3 years. 48/82 (59%) developed hand symptoms within the defined peri-menopausal period (FMP ± 4 years), whilst some women developed their symptoms before or after (range -25, 30 years). In women who discontinued HRT prior to symptom onset, the median time from HRT cessation to onset of hand symptoms was 6 months. Past HRT users were older at hand symptom onset than women who had not taken HRT [coeff.4.7 years (0.92, 8.39); P = 0.015]. This study adds to evidence associating the menopause/sex hormone deficiency with hand OA symptom onset in a sizeable subgroup of women (but not all). HRT use/cessation appears to influence the timing of onset of hand OA symptoms. It is not possible to interpret from this type of study whether sex hormone deficiency is causative of disease or modulates its symptoms. It is also not possible to judge whether painful hand osteoarthritis in post-menopausal women is a subtype of disease. Further investigation is indicated of sex-specific subtypes and potential for personalised medicine for post-menopausal women with hand osteoarthritis, as a clearly definable high-risk subgroup.

Abstract B083: The associations of breast density, hormone use, family history, reproductive and lifestyle factors with triple negative breast cancer: a systematic review and meta-analysis

Abstract Background: Triple negative breast cancer (TNBC) has poor prognosis compared to other breast cancer subtypes. Objectives: This systematic review and meta-analysis examines whether established breast cancer risk factors are associated with TNBC in adult females.Data Sources: Studies were searched on EMBASE, Medline, SCOPUS and grey literature with no limit on the date of publication. The search string included MeSH terms of the exposures of interest and TNBC. References of included studies were also searched. Study Selection: The exposures of interest included parity, breastfeeding, duration of breastfeeding, age at menarche, age at first live birth, oral contraceptive (OCP) use, duration of OCP use, use of hormone replacement therapy (HRT), family history, body mass index (BMI), alcohol use, smoking and breast density. Studies that compared exposures of interest between women diagnosed with TNBC versus cancer-free women.Main outcomes and Measures: The main outcome of interest was TNBC. The effect measures, weighted odds ratios, were estimated from random effects models. Sensitivity analyses stratified by menopausal status and using the leave one out meta-analysis (LOOM) method were performed.Data Extraction and Synthesis: Data extraction and synthesis was performed as per PRISMA guidelines. Four reviewers independently screened the search results in a blinded manner and conflicts were resolved by discussion. Study quality was determined using the Newcastle-Ottawa scale for case control studies and cohort studies. Data extraction was performed independently by four reviewers and one reviewer checked 30% of work of each other reviewer. Odds ratios were extracted and data were meta-analyzed using a random effects model. Results: Thirty-three studies were included. Family history, longer duration of oral contraceptive use, and higher breast density were significantly associated with increased risk for TNBC, and later age at menarche and breastfeeding were protective against TNBC. Later age at first birth was protective against TNBC. Parity, HRT, alcohol, smoking, and BMI were not significantly associated with risk for TNBC. Conclusion: These findings further clarify differences in etiology between ER/PR+HER2- and TNBC, highlighting the need to identify additional actionable risk factors for TNBC to improve prevention and early detection of these poor prognosis breast tumors. Citation Format: Nitya Kumar, Sarah Ehsan, Shahana Banerjee, Claudia Fernandez Perez, Isabelle Lhuilier, Jilian Neuner, Tara-Friebel Klinger, Bindhu Nair, Sara Anjum Niinuma, Shivangi Nampoothiri, Anne Marie McCarthy. The associations of breast density, hormone use, family history, reproductive and lifestyle factors with triple negative breast cancer: a systematic review and meta-analysis [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B083.

Investigating the synergistic effects of hormone replacement therapy, apolipoprotein E and age on brain health in the UK Biobank.

Global prevalence of Alzheimer's Disease has a strong sex bias, with women representing approximately two-thirds of the patients. Yet, the role of sex-specific risk factors during midlife, including hormone replacement therapy (HRT) and their interaction with other major risk factors for Alzheimer's Disease, such as apolipoprotein E (APOE)-e4 genotype and age, on brain health remains unclear. We investigated the relationship between HRT (i.e., use, age of initiation and duration of use) and brain health (i.e., cognition and regional brain volumes). We then consider the multiplicative effects of HRT and APOE status (i.e., e2/e2, e2/e3, e3/e3, e3/e4 and e4/e4) via a two-way interaction and subsequently age of participants via a three-way interaction. Women from the UK Biobank with no self-reported neurological conditions were included (N = 207,595 women, mean age = 56.25 years, standard deviation = 8.01 years). Generalised linear regression models were computed to quantify the cross-sectional association between HRT and brain health, while controlling for APOE status, age, time since attending centre for completing brain health measure, surgical menopause status, smoking history, body mass index, education, physical activity, alcohol use, ethnicity, socioeconomic status, vascular/heart problems and diabetes diagnosed by doctor. Analyses of structural brain regions further controlled for scanner site. All brain volumes were normalised for head size. Two-way interactions between HRT and APOE status were modelled, in addition to three-way interactions including age. Results showed that women with the e4/e4 genotype who have used HRT had 1.82% lower hippocampal, 2.4% lower parahippocampal and 1.24% lower thalamus volumes than those with the e3/e3 genotype who had never used HRT. However, this interaction was not detected for measures of cognition.No clinically meaningful three-way interaction between APOE, HRT and age was detected when interpreted relative to the scales of the cognitive measures used and normative models of ageing for brain volumes in this sample. Differences in hippocampal volume between women with the e4/e4 genotype who have used HRT and those with the e3/e3 genotype who had never used HRT are equivalent to approximately 1-2 years of hippocampal atrophy observed in typical health ageing trajectories in midlife (i.e., 0.98%-1.41% per year). Effect sizes were consistent within APOE e4/e4 group post hoc sensitivity analyses, suggesting observed effects were not solely driven by APOE status and may, in part, be attributed to HRT use. Although, the design of this study means we cannot exclude the possibility that women who have used HRT may have a predisposition for poorer brain health.

Should hormone replacement therapy (any route of administration) be considered in all postmenopausal women with lower urinary tract symptoms? Report from the ICI-RS 2023.

This International Consultation on Incontinence-Research Society report aims to summarize the evidence and uncertainties regarding the use of hormone replacement therapy by any route in the management of lower urinary tract symptoms (LUTS) including recurrent urinary tract infections (rUTI), with a review of special considerations for the elderly. Research question proposals to further this field have been highlighted. An overview of the existing evidence, guidelines, and consensus regarding the use of topical or systemic estrogens in the management of LUTS. There are currently evidence and recommendations to offer topical estrogens to postmenopausal women with overactive bladder symptoms as well as postmenopausal women with rUTIs. Systemic estrogens however have been shown in a meta-analysis to have a negative effect on LUTS and, therefore are not currently recommended. Although available evidence and recommendations exist for the use of topical estrogens, few women are commenced on these in primary care. There remain large gaps still within our knowledge of the use of estrogens within the management of LUTS, particularly on when it should be commenced, the length of time treatment should be continued for, and barriers to prescribing.

Explaining variability in early stages of [18F]-flortaucipir tau-PET binding: Focus on sex differences.

Female sex is associated with increased [18F]-flortaucipir signal, which may be affected by amyloid pathology, age, and off-target binding in skull and meninges. In this cross-sectional study comprising 52 females and 52 matched males, we examined sex-related differences in regional tau-positron emission tomography (PET) with and without considering off-target binding. We assessed the respective contributions of sex, age, amyloid-PET burden, and off-target binding to tau-PET signal. We explored associations between age at menopause and hormone replacement therapy (HRT) use with regional tau-PET signals. Female sex was associated with increased regional tau both independently and interactively with amyloid, but amyloid-independent associations were largely reduced when controlling for off-target binding. Age but not age*sex interactions explained a small but significant amount of tau-PET signal in temporoparietal regions. Considering the sample size and limited range of amyloid-PET burden, no clear associations between regional tau-PET signals and age at menopause or HRT use could be found. Female sex is associated with increased [18F]-flortaucipir signal mainly through its interaction with amyloid.

Hormone replacement therapy in gynecological cancer survivors and BRCA mutation carriers: a MITO group survey.

Early iatrogenic menopause in gynecological cancer survivors and BRCA mutation (BRCAm) carriers undergoing risk-reducing salpingo-oophorectomy (RRSO) is a major health concern. Hormone replacement therapy (HRT) is the most effective remedy, but remains underused in clinical practice. The Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) group promoted a national survey to investigate the knowledge and attitudes of healthcare professionals regarding the prescription of HRT. The survey consisted of a self-administered, multiple-choice 45-item questionnaire, available online to all MITO members for 2 months starting from January 2022. A total of 61 participants completed the questionnaire (47 out of 180 MITO centers; compliance: 26.1%). Most respondents were female (73.8%), younger than 50 years (65.6%), and gynecologic oncologists (55.7%), working in public general hospitals (49.2%). An 84.4% of specialists actively discuss HRT with patients and 51.0% of patients ask the specialist for an opinion on HRT. The rate of specialists globally in favor of prescribing HRT was 22.9% for ovarian cancer, 49.1% for cervical cancer, and 8.2% for endometrial cancer patients. Most respondents (70.5%) believe HRT is safe for BRCA-mutated patients after RRSO. Nearly 70% of physicians prescribe systemic HRT, while 23.8% prefer local HRT. Most specialists recommend HRT for as long as there is a benefit and generally for up to 5 years. Real-world data suggest that many healthcare professionals still do not easily prescribe HRT for gynecological cancer survivors and BRCA mutation carriers after RRSO. Further efforts are required to implement the use of HRT in clinical practice and to support both clinicians in recommending HRT and patients in accepting it.

Does exogenous hormonal therapy affect the risk of glioma among females: A systematic review and meta-analysis.

The effect of exogenous hormone replacement therapy (HRT) and oral contraceptive pills (OCPs) on glioma risk in females is unclear despite numerous studies; hence, we conducted a meta-analysis to evaluate this relationship. Studies investigating the impact of exogenous female hormones on glioma risk were retrieved by searching 4 databases from inception until September 2022. Articles of any design, such as case-control and cohort studies, proving the relative risk (RR), odds ratio (OR), or hazard ratio were included. Summary OR values were calculated using a random effects model. Both HRT and OCP use of any duration decreased the risk of developing glioma [HRT OR = 0.78, 95% CI 0.66-0.91, P = .00; OCP: OR = 0.80, 95% CI 0.67-0.96, P = .02]. When stratified by duration of use, HRT use >1 year significantly reduced glioma risk (<1 year: OR = 0.82, 95% CI 0.63-1.07, P = 0.15; 1-5 years: OR = 0.79, 95% CI 0.67-0.92, P = .00; 5-10 years: OR = 0.80, 95% CI 0.66-0.97, P = .02; >10 years: OR = 0.69, 95% CI 0.54-0.88, P = .00). In contrast, only OCP use for >10 years significantly reduced glioma risk (<1 year: OR = 0.72, 95% CI 0.49-1.05, P = .09; 1-5 years: OR = 0.88, 95% CI 0.72-1.02, P = .09; 5-10 years: OR = 0.85, 95% CI 0.65-1.1, P = 0.21; >10 years: OR = 0.58, 95% CI 0.45-0.74, P = .00). Our pooled results strongly suggest that sustained HRT and OCP use is associated with reduced risk of glioma development.

Effect of baseline oestradiol serum concentration on the efficacy of anastrozole for preventing breast cancer in postmenopausal women at high risk: a case-control study of the IBIS-II prevention trial

An increased risk of breast cancer is associated with high serum concentrations of oestradiol and testosterone in postmenopausal women, but little is known about how these hormones affect response to endocrine therapy for breast cancer prevention or treatment. We aimed to assess the effects of serum oestradiol and testosterone concentrations on the efficacy of the aromatase inhibitor anastrozole for the prevention of breast cancer in postmenopausal women at high risk. In this case-control study we used data from the IBIS-II prevention trial, a randomised, controlled, double-blind trial in postmenopausal women aged 40-70 years at high risk of breast cancer, conducted in 153 breast cancer treatment centres across 18 countries. In the trial, women were randomly assigned (1:1) to receive anastrozole (1 mg/day, orally) or placebo daily for 5 years. In this pre-planned case-control study, the primary analysis was the effect of the baseline oestradiol to sex hormone binding globulin (SHBG) ratio (oestradiol-SHBG ratio) on the development of all breast cancers, including ductal carcinoma in situ (the primary endpoint in the trial). Cases were participants in whom breast cancer was reported after trial entry and until the cutoff on Oct 22, 2019, and who had valid blood samples and no use of hormone replacement therapy within 3 months of trial entry or during the trial. For each case, two controls without breast cancer were selected at random, matched on treatment group, age (within 2 years), and follow-up time (at least that of the matching case). For each treatment group, we applied a multinominal logistic regression likelihood-ratio trend test to assess what change in the proportion of cases was associated with a one-quartile change in hormone ratio. Controls were used only to determine quartile cutoffs. Profile likelihood 95% CIs were used to indicate the precision of estimates. A secondary analysis also investigated the effect of the baseline testosterone-SHBG ratio on breast cancer development. We also assessed relative benefit of anastrozole versus placebo (calculated as 1 - the ratio of breast cancer cases in the anastrozole group to cases in the placebo group). The trial was registered with ISRCTN (number ISRCTN31488319) and completed recruitment on Jan 31, 2012, but long-term follow-up is ongoing. 3864 women were recruited into the trial between Feb 2, 2003, and Jan 31, 2012, and randomly assigned to receive anastrozole (n=1920) or placebo (n=1944). Median follow-up time was 131 months (IQR 106-156), during which 85 (4·4%) cases of breast cancer in the anastrozole group and 165 (8·5%) in the placebo group were identified. No data on gender, race, or ethnicity were collected. After exclusions, the case-control study included 212 participants from the anastrozole group (72 cases, 140 controls) and 416 from the placebo group (142 cases, 274 controls). A trend of increasing breast cancer risk with increasing oestradiol-SHBG ratio was found in the placebo group (trend per quartile 1·25 [95% CI 1·08 to 1·45], p=0·0033), but not in the anastrozole group (1·06 [0·86 to 1·30], p=0·60). A weaker effect was seen for the testosterone-SHBG ratio in the placebo group (trend 1·21 [1·05 to 1·41], p=0·011), but again not in the anastrozole group (trend 1·18 [0·96 to 1·46], p=0·11). A relative benefit of anastrozole was seen in quartile 2 (0·55 [95% CI 0·13 to 0·78]), quartile 3 (0·54 [0·22 to 0·74], and quartile 4 (0·56 [0·23 to 0·76]) of oestradiol-SHBG ratio, but not in quartile 1 (0·18 [-0·60 to 0·59]). These results suggest that serum hormones should be measured more routinely and integrated into risk management decisions. Measuring serum hormone concentrations is inexpensive and might help clinicians differentiate which women will benefit most from an aromatase inhibitor. Cancer Research UK, National Health and Medical Research Council (Australia), Breast Cancer Research Foundation, and DaCosta Fund.

The effectiveness of estrogen therapy and aerobic exercise combined with resistance training therapy in postmenopausal womens osteoporosis

Postmenopausal osteoporosis (PMOP) usually happens five to ten years following a womans menopause, and some women over 50 in China suffer from PMOP. Hormone replacement therapy (HRT) and aerobics combined with resistance training are the two promising osteoporosis interventions, but few studies have compared their efficacy. The mechanisms by which exercise treatment and hormone replacement therapy affect bone mineral density (BMD) are examined in this review and other health parameters in postmenopausal osteoporosis patients. As studied in this paper, estrogen improves osteoporosis. However, risks such as venous thromboembolism limit the long-term use of HRT. In terms of exercise therapy, a direct comparison of aerobic exercise combined with resistance exercise and HRT showed that supervised exercise improved BMD more than HRT and that exercise also boosted metabolism and avoided the risks of HRT. In conclusion, aerobic and resistance training provides a safer alternative to HRT for managing postmenopausal osteoporosis, and further studies should optimize exercise regimens.