Breast Cancer In Premenopausal Women Research Articles

Trends of breast cancer in premenopausal women over two decades

Trends of breast cancer in premenopausal women over two decades

A review of phase III clinical trials of CDK4/6 inhibitor combination therapy in premenopausal women.

141 Background: Clinical guidelines for the treatment of hormone receptor–positive (HR+), HER2− advanced breast cancer (ABC) are similar regardless of menopausal status, except for the role of ovarian suppression. However, breast cancers in premenopausal women frequently have an aggressive phenotype and a distinct underlying disease biology unaffected by ovarian suppression. Methods: We compared published trial designs, baseline characteristics, and efficacy and safety results of Phase 3 trials of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors including premenopausal women with HR+, HER2− ABC. Results: The MONALEESA-7 trial (NCT02278120) investigated ribociclib (or placebo) with a nonsteroidal aromatase inhibitor or tamoxifen + goserelin ovarian suppression in premenopausal women with ≤1 line of prior chemotherapy for ABC (N = 672); 40% had de novo metastases. Median progression-free survival (PFS) was 23.8 vs 13.0 months with ribociclib (n = 335) vs placebo (n = 337). In the PALOMA-3 trial (NCT01942135), 108 of 521 patients were premenopausal and treated with palbociclib (n = 72) or placebo (n = 36) + fulvestrant + goserelin; 75% had prior endocrine therapy (ET) or chemotherapy for ABC. Median PFS in the palbociclib vs placebo group was 9.5 vs 5.6 months. Adverse events common to both ribociclib and palbociclib ( > 30%) were neutropenia, leukopenia, and nausea. The MONARCH 2 trial (NCT02107703) evaluated abemaciclib (or placebo) with fulvestrant in 669 women with no prior chemotherapy for ABC (38% had 1 line of ET for ABC). In the premenopausal subset (abemaciclib, n = 72; placebo, n = 42; all with ovarian suppression), abemaciclib prolonged PFS (hazard ratio, 0.415 [95% confidence interval, 0.246–0.698]). Conclusions: While trial and patient characteristics differed substantially, safety and efficacy established in the MONALEESA-7 trial of premenopausal women and premenopausal subsets of the PALOMA-3 and MONARCH 2 trials support the activity and use of CDK4/6 inhibitor combination therapy in these patients. The treatment benefit observed in these trials was consistent with that in Phase 3 trials of postmenopausal women with HR+, HER2− ABC treated with CDK4/6 inhibitor combination therapy.

Targeted Therapy for Premenopausal Women with HR+, HER2− Advanced Breast Cancer: Focus on Special Considerations and Latest Advances

The incidence of advanced breast cancer in premenopausal women is increasing, and breast cancer in younger women is often more aggressive and has a worse prognosis compared with breast cancer in older women. Premenopausal women with hormone receptor-positive (HR+) breast cancer are frequently under-represented in clinical trials, and treatment strategies in the premenopausal setting are usually extrapolated from data from postmenopausal patients, with the addition of ovarian function suppression to endocrine therapy in HR+ disease. However, the underlying biology of breast cancer in premenopausal women can be different from postmenopausal women, and treatment strategies should ideally be specifically tested in premenopausal patients. Recent phase III trials have now investigated cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in premenopausal patients with HR+, HER2- advanced breast cancer: Palbociclib and abemaciclib have been tested in a subset of premenopausal patients in the PALOMA-3 and MONARCH-2 studies, and ribociclib has been tested in the phase III MONALEESA-7 trial, which was entirely dedicated to premenopausal women. This comprehensive review summarizes the differences in the biology of HR+, HER2- breast cancer in the premenopausal population compared with the postmenopausal population; discusses special considerations for treatment of premenopausal women; and reviews the evidence from clinical trials investigating endocrine therapy, other targeted treatments, and ovarian function suppression in the HR+, HER2- advanced breast cancer setting. Clin Cancer Res; 24(21); 5206-18. ©2018 AACR.

Ribociclib Plus Endocrine Therapy in Premenopausal Women

Ribociclib Plus Endocrine Therapy in Premenopausal Women

Thyroid hormones and breast cancer association according to menopausal status and body mass index

BackgroundThyroxine (T4) has been positively associated with tumor cell proliferation, while the effect of triiodothyronine (T3) on cell proliferation has not been well-established because it differs according to the type of cell line used. In Mexico, it has been reported that 14.5% of adult women have some type of thyroid dysfunction and abnormalities in thyroid function tests have been observed in a variety of non-thyroidal illnesses, including breast cancer (BC). These abnormalities might change with body mass index (BMI) because thyroid hormones are involved in the regulation of various metabolic pathways and probably by menopausal status because obesity has been negatively associated with BC in premenopausal women and has been positively associated with BC in postmenopausal women.MethodsTo assess the association between serum thyroid hormone concentration (T4 and T3) and BC and the influence of obesity as an effect modifier of this relationship in premenopausal and postmenopausal women, we measured serum thyroid hormone and thyroid antibody levels in 682 patients with incident breast cancer (cases) and 731 controls, who participated in a population-based case-control study performed from 2004 to 2007 in three states of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3) stratifying by menopausal status and body mass index (BMI), and adjusted for other health and demographic risk factors using logistic regressions models.ResultsHigher serum total T4 (TT4) concentrations were associated with BC in both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01–11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17–3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while the opposite was observed in postmenopausal women. The significance of the effect modification was marginal (p = 0.059) in postmenopausal women and was not significant in premenopausal women (p = 0.22). Lower TT3 concentrations were associated with BC in both premenopausal and postmenopausal women and no effect modification was observed.ConclusionsThere is a strong association between BC and serum concentrations of TT3 and TT4; this needs to be further investigated to understand why it happens and how important it is to consider these alterations in treatment.

Abdominal Adiposity and Physical Inactivity Are Positively Associated with Breast Cancer: A Case-Control Study.

Objective To examine whether breast cancer is associated with body composition and level of physical activity, considering the menstrual status. Methods This was a case-control study with 116 women recently diagnosed with breast cancer and 226 controls. Body composition was assessed by dual-energy X-ray absorptiometry, and cardiometabolic risk was assessed by conicity index and waist-to-height ratio. The short version of the International Physical Activity Questionnaire was used to estimate the level of physical activity. All analyses were adjusted for age and BMI. Results The total body fat percentage, android body fat, android-gynoid ratio, and waist circumference were positively associated (p < 0.05), whereas the percentage of lean body mass (p <0.05) and the level of physical activity (p < 0.01) were inversely associated with breast cancer in premenopausal women. Among postmenopausal women, physical activity decreased the chance of developing breast cancer by 49% (95% CI = 0.29 to 0.92, p = 0.02). Conclusion A low percentage of lean body mass and high abdominal adiposity in the premenopausal period increase the chances of developing breast cancer. Regular physical activity is inversely associated with breast cancer in pre- and postmenopausal women.

PO-310 Genomic features of premenopausal breast cancers in latin american women: the PRECAMA study

Introduction In Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we have characterised the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study on breast cancer in premenopausal women. Material and methods Pathological tumour tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6 and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analysed by exome sequencing to identify somatic mutational signatures. Results and discussions The majority of cases were positive for ER or PR (168/233; 72%) and 21% of cases were triple negative (TN), mainly of basal type. Most tumours were positive for Ki67 (189/233; 81%). In 126 sequenced cases, TP53 and PIK3CA were the most frequently mutated genes (32.5% and 21.4%, respectively), followed by AKT1 (9.5%). TP53 mutations were more frequent in HER2-enriched and TN IHC subtypes, while PIK3CA/AKT1 mutations were more frequent in ER-positive tumours, as expected. Interestingly, a higher proportion of G:C>T:A mutation type was observed in TP53 gene in PRECAMA cases compared to TCGA and METABRIC breast cancer series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signalling transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways. Conclusion This pilot study on PRECAMA tumours gives a preview of the molecular features of premenopausal BC in LA. Although the overall mutation burden was as expected from data in other populations, mutational patterns observed in TP53 and exome-wide suggested possible differences in mutagenic processes giving rise to these tumours compared to other populations. Further omics analyses of a larger number of cases in the near future will allow investigating relationships between these molecular features and risk factors.

C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells

BackgroundTamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance.MethodsMTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence. SiRNA was used to examine the function of HER2 in of BT474 cells. An in vivo xenograft animal model was established to examine the role of c-Cbl in tumor growth.ResultsMTT and colony formation assay showed that BT474 cells are resistant to tamoxifen and T47D cells are sensitive to tamoxifen. Immunoprecipitation experiments revealed ER-c-Src-HER2 complex formation in BT474 cells but not in T47D cells. However, ER-c-Src-HER2 complex formation was detected after overexpressing HER2 in T47D cells and these cells were more resistant to tamoxifen. HER2 knockdown by siRNA in BT474 cells reduced ER-c-Src-HER2 complex formation and reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was also disrupted and tamoxifen resistance was reversed in BT474 cells by the c-Src inhibitor PP2 and HER2 antibody trastuzumab. Nystatin, a lipid raft inhibitor, reduced ER-c-Src-HER2 complex formation and partially reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was disrupted by overexpression of c-Cbl but not by the c-Cbl ubiquitin ligase mutant. In addition, c-Cbl could reverse tamoxifen resistance in BT474 cells, but the ubiquitin ligase mutant had no effect. The effect of c-Cbl was validated in BT474 tumor-bearing nude mice in vivo. Immunofluorescence also revealed ER-c-Src-HER2 complex formation was reduced in tumor tissues of nude mice with c-Cbl overexpression.ConclusionsOur results suggested that c-Cbl can reverse tamoxifen resistance in HER2-overexpressing breast cancer cells by inhibiting the formation of the ER-c-Src-HER2 complex.

P-138 - Redox status in breast tumor and associated adipose tissue - interplay between obesity and malignancy

Evidence linking obesity to breast cancer in premenopausal women remains inconclusive. We aimed to reveal redox status related to malignant phenotype and its relationship with obesity. To this end, premenopausal women with breast tumors were divided into four groups: normal-weight (non-obese) with benign tumors, obese with benign tumors, non-obese with malignant tumors and obese with malignant tumors. We examined activity and protein expression of main antioxidant defense (AD) enzymes (copper, zinc- and manganese- superoxide dismutase, catalase and glutathione peroxidase) in breast tumor tissue and tumor-associated adipose tissue. Activity and protein expression of AD enzymes were generally increased in malignant tumors of non-obese and obese women, in comparison to their respective benign counterparts. In tumor-associated adipose tissue of non-obese women, activity and protein expression of AD enzymes were increased in subjects with malignant tumors in comparison to those with benign tumors. In conclusion, the effect of malignancy on the redox signature of tumor tissue is evident in both non-obese and obese subjects, while in adipose tissue the effect is pronounced mostly in non-obese subjects, suggesting redox sensitive interplay between obesity and cancer.

Adiposity at Age 10 and Mammographic Density among Premenopausal Women.

Although childhood adiposity is inversely associated with breast cancer risk, the association of childhood adiposity with mammographic density in premenopausal women has not been adequately studied. We analyzed data from 365 premenopausal women who came in for screening mammography at Washington University (St. Louis, MO) from 2015 to 2016. Body size at age 10 was self-reported using somatotype pictogram. Body mass index (BMI) at age 10 was imputed using data from Growing Up Today Study. Volpara software was used to evaluate volumetric percent density (VPD), dense volume (DV), and nondense volume (NDV). Adjusted multivariable linear regression models were used to evaluate the associations between adiposity at age 10 and mammographic density measures. Adiposity at age 10 was inversely associated with VPD and positively associated with NDV. A 1 kg/m2 increase in BMI at age 10 was associated with a 6.4% decrease in VPD, and a 6.9% increase in NDV (P < 0.001). Compared with women whose age 10 body size was 1 or 2, women with body size 3 or 4 had a 16.8% decrease in VPD and a 26.6% increase in NDV, women with body size 5 had a 32.2% decrease in VPD and a 58.5% increase in NDV, and women with body sizes ≥6 had a 47.8% decrease in VPD and a 80.9% increase in NDV (P < 0.05). The associations were attenuated, but still significant after adjusting for current BMI. Mechanistic studies to understand how childhood adiposity influences breast development, mammographic density, and breast cancer in premenopausal women are needed. Cancer Prev Res; 11(5); 287-94. ©2018 AACR.

Obesity and breast cancer in premenopausal women: Current evidence and future perspectives.

There is raising evidence reporting an increased incidence of breast cancer over the past decades. Every year approximately 1.4 million new cases of breast cancer are diagnosed worldwide, with a mortality rate of approximately 450,000/year. Out of these cases, 6.6% are diagnosed in premenopausal women with a median age at diagnosis of 40 years: in premenopausal women breast cancer seems to be more aggressive than in post-menopausal women. Obesity has been reported to increase the risk of developing breast cancer and to worsen the prognosis. This seems to be due to several obesity-related mechanisms. Insulin resistance that often occurs with obesity may results in compensatory hyperinsulinemia. Insulin cross-binds insulin-like growth factor-I receptors expressed on breast cells, resulting in proliferative stimuli on breast cancer cells. Besides, hyperinsulinemia up-regulates the growth hormone receptor (GHR) thus increasing GHR stimulation and resulting in an increased hepatic IGF-I synthesis. Moreover, insulin decreases the hepatic expression of binding proteins of IGF-I, such as insulin-like growth factor binding proteins (IGFBP)-1 and IGFBP-2, thus leading to high circulating and bioavailable free IGF-I. Additionally, obesity is associated to chronic low-grade inflammation that has been reported to be an additional stimulus for tumor growth. This review shows the current evidence regarding to the association of obesity and breast cancer in premenopausal state focusing on both human and basic studies; showing that the obesity is a risk factor for breast cancer also among premenopausal women, especially for the molecular subtype Triple Negative Breast Cancer.

Night shift work and breast cancer: a pooled analysis of population-based case-control studies with complete work history.

Night shift work has been suspected to increase breast cancer risk but epidemiological studies have been inconsistent due to heterogeneous assessment of exposure to night work. To overcome this limitation, we pooled data of five population-based case-control studies from Australia, Canada, France, Germany, and Spain into a single harmonized dataset using a common definition of night work including 6093 breast cancer cases and 6933 population controls. The odds ratio for breast cancer in women who ever worked at night for at least 3 h between midnight and 5 a.m. as compared to never night workers was 1.12 (95% CI 1.00-1.25). Among pre-menopausal women, this odds ratio was 1.26 [1.06-1.51], increasing to 1.36 [1.07-1.74] for night shifts≥10h, 1.80 [1.20-2.71] for work≥3 nights/week, and 2.55 [1.03-6.30] for both duration of night work≥10years and exposure intensity≥3 nights/week. Breast cancer risk in pre-menopausal women was higher in current or recent night workers (OR=1.41 [1.06-1.88]) than in those who had stopped night work more than 2years ago. Breast cancer in post-menopausal women was not associated with night work whatever the exposure metric. The increase in risk was restricted to ER+ tumors, particularly those who were both ER+ and HER2+. These results support the hypothesis that night shift work increases the risk of breast cancer in pre-menopausal women, particularly those with high intensity and long duration of exposure. Risk difference between pre- and post-menopausal women deserves further scrutiny.

Surgical Oophorectomy is Ineffective Therapy in Women with Hormone-Receptor Positive Breast Cancer Who are in Historical, but Low-Progesterone Luteal Phase

The hormonal biology of the menstrual cycle has major relevance in the treatment of hormone-sensitive breast cancer. There are 500,000 new cases of hormone-receptor positive breast cancer in premenopausal women annually; 80% of these are among women in low- and middle-income countries. Surgical oophorectomy should play a major role in the treatment of these women. New data from two phase III clinical trials show that women who are in historical luteal phase, but have low progesterone levels at the times of their oophorectomy surgeries benefit little from this intervention. The unique sequence of hormonal signaling to micro-metastases which occurs in this situation offers a logical explanation for this observation. Because surgical oophorectomy is a safe and widely practical and affordable intervention, this new observation and explanation deserves the attention of the practicing global surgical community. Universal application of surgical oophorectomy treatment could save 100,000 lives of young women with breast cancer each year.

108P - Does non-adherence result in worse clinical outcomes for hormone receptor-positive and HER2-negative metastatic breast cancer in premenopausal women?

108P - Does non-adherence result in worse clinical outcomes for hormone receptor-positive and HER2-negative metastatic breast cancer in premenopausal women?

Does obesity modify the relationship between physical activity and breast cancer risk?

With only 5-10% of breast cancer cases attributed to genetic inheritance, prevention efforts have focused on modifiable risk factors. Physical activity plays a role in reducing breast cancer risk; however, the interaction between physical activity and other modifiable risk factors, such as obesity, has received little attention. A systematic review and meta-analysis was conducted of studies examining the relationship between physical activity and breast cancer and how it may be modified by body mass index (BMI). A total of 29 papers were included: 18 were cohort and 11 were case-control studies. Overall, a significant reduction in the relative risk of breast cancer was found in postmenopausal women with high versus low levels of physical activity for women with a BMI <25kg/m2 (RR 0.85, 95% CI 0.79, 0.92) and ≥25kg/m2 (RR 0.87, 95% CI 0.81, 0.93) but not ≥30kg/m2 (RR: 0.93, 95% CI 0.76, 1.13). Physical activity was not associated with a significant reduction in risk of breast cancer in premenopausal women in any BMI group. The results of this meta-analysis suggest that physical activity is associated with a larger breast cancer risk reduction among women who are normal weight or overweight than among women who are obese. Since the included studies used diverse methods for assessment of physical activity and categories of BMI, results should be interpreted with caution and additional work is needed.

Surgical ovarian ablation for hormone receptor positive primary breast cancer in premenopausal women.

e12536 Background: Ovarian ablation is increasingly used to complement endocrine therapy in select premenopausal women with hormone-receptor positive (HR+) breast cancer (BC). It can be achieved by either medical ovarian suppression (OS) or therapeutic bilateral salpingo-oophorectomy (BSO). We sought to investigate trends of therapeutic BSO in premenopausal patients at our institution. Methods: Premenopausal women with HR+ primary BC diagnosed from 2010-2014 were identified in our prospectively maintained BC database. Patients with confirmed BRCA1/2 mutations were excluded. Distribution of patient and disease characteristics between treatment groups were assessed using univariate logistic regression analyses. Surgical details and complications were extracted from our surgical database. Results: We identified 2,854 eligible patients; 2,113 (74%) received endocrine therapy without ovarian ablation, 246 (9%) received endocrine therapy plus medical OS, 180 (6%) underwent additional BSO, and 315 (11%) did not receive endocrine therapy at the time of analysis. Independent predictors for undergoing ovarian ablation were younger age (OR 0.98; 95%CI, 0.96-0.99; p &lt; 0.001), higher grade (grade 3 vs 1: OR 3.17; 95%CI, 1.70-5.90; grade 2 vs 1: OR 3.13; 95%CI, 1.64-5.95; p &lt; 0.001), lymph node involvement (OR 1.46; 95%CI, 1.19-1.80; p &lt; 0.001), and higher AJCC stage as well as de novo metastatic BC (II vs I: OR = 1.35; 95%CI, 1.03-1.76; III vs I: OR 2.57; 95%CI, 1.86-3.55; IV vs I: OR 19.69; 95%CI, 12.76-30.39; p &lt; 0.001). Among patients who underwent ovarian ablation, patients of younger age (1.04; 95%CI, 1.01-1.07; p = 0.009) and with metastatic BC (stage IV vs I: OR 0.36; 95%CI, 0.20-0.68; p = 0.007) were less likely to undergo BSO than OS. In 180 patients undergoing BSO, five adverse events were noted: two grade 1, two grade 2, and one grade 3 complication. Conclusions: Premenopausal women with HR+ BC with high-risk features or metastatic disease were more likely to undergo ovarian ablation at our institution. Surgical ovarian ablation is a safe alternative, with low complication rates. Understanding patient preferences, side effects, and quality of life implications will help guide personalized treatment decisions.

The Epidemiological Challenges of Breast Cancer among Premenopausal Women in Limited Resource Settings.

Breast cancer is the most common malignant tumor among women of reproductive age and is also the most costly according to European reports. In this context, the aim of the present review is to identify factors that make breast cancer in premenopausal women an epidemiological challenge in developing countries. Epidemiological aspects of breast cancer, including risk factors, early detection methods, and treatment, are addressed. Breast cancer in premenopausal women should be included in the political and strategic agendas in developing countries to direct the necessary resources for prevention, detection, and control.

Surgical oophorectomy: a primary option in adjuvant treatment of premenopausal breast cancer

Globally, there are 500,000 annual new cases of hormone-sensitive breast cancer in premenopausal women; 400,000 of these occur in women in low and middle income countries (LMIC). With optimal adjuvant therapy, fully one third more than the half of women who might survive with primary surgery alone-more than 80%, could survive 10 years. Affordability and practicality of treatment profoundly affect global practice and these do not characterize the current standards of care – LHRH agonist plus tamoxifen or an aromatase inhibitor.Surgical oophorectomy plus tamoxifen is a safe, efficient and affordable, patient-centered and equitable adjuvant treatment, long considered equivalent to that from LHRH agonist plus tamoxifen treatment. New data additionally suggest that women, who are in extended follicular phase of their cycles at the time of surgery, benefit much less from this treatment, and women who are in normal progesterone-confirmed follicular or luteal phases, benefit more than unselected or LHRH-treated women. New data also show that surgical oophorectomy plus tamoxifen is associated with no loss of bone mineral density at the hip, and loss for only a year in the lumbar spine.The dominance of a business model for medicine, the narrow perspective and single metric-efficacy focus of guideline creation, and limited understanding of the practice of medicine for poor women worldwide, appear to be contributing to the social injustice of not offering women the option of surgical oophorectomy instead of LHRH treatment. 100,000 women a year could be saved. Further research investigating outcomes associated with the timing of surgical oophorectomy is strongly justified.

HR+/Her2- breast cancer in pre-menopausal women: The impact of younger age on clinical characteristics at diagnosis, disease management and survival

Young women (20–39 years-old) with breast cancer are diagnosed with more aggressive tumours and consequently have poorer survival. However, there is an evidence gap as to whether age has an independent effect on survival of pre-menopausal women diagnosed with HR+/Her2- tumours. The aim of this population-based study was to compare characteristics at diagnosis, determinants of treatment and survival in women aged 20–39 and 40–49 years diagnosed with HR+/Her2- tumours. From the National Cancer Registry Ireland, we identified women aged 20–49 diagnosed with a first invasive HR+/Her2- breast cancer during 2002–2008. Women aged 20–39 were compared to those aged 40–49 years. Poisson regression with robust error variance was used to explore the impact of age on treatment receipt. Associations between age and survival from all causes was investigated using Cox models. In multivariate models, women aged 20–39 significantly more often having no cancer-directed surgery (IRR=1.49, 95%CI 1.07, 2.08). In those having surgery, younger age was associated with significantly higher likelihood of receiving chemotherapy; age was not associated with receipt of adjuvant radiotherapy or endocrine therapy. Women aged 20–39 undergoing surgery were significantly more likely to die than women aged 40–49 (HR=1.84, 95%CI: 1.31, 2.59). Age is an independent prognostic factor in younger women diagnosed with HR+/Her2- breast cancer, supporting the hypothesis that breast cancer in women under 40 has more aggressive behaviour, even within HR+/Her2- tumours. Future research should explore the reasons for poorer survival in order to inform strategies to improve outcomes in this age group.

Chemotherapy-Induced Amenorrhea and Menopause Symptoms in Women With Breast Cancer

Chemotherapy is a common adjuvant therapy for breast cancer that improves survival rates by killing residual cancer cells. However, this intervention may damage the germ cells within the ovary and interrupt the menstrual cycle, ultimately leading to chemotherapy-induced amenorrhea (CIA). The incidence of CIA depends on how broadly this term is defined. Around 75% of premenopausal breast cancer women treated with chemotherapy will develop CIA. Age, having a relatively long chemotherapy cycle duration, being estrogen-receptor positive, and using Tamoxifen all increase the risk of CIA. Although CIA may be associated with better prognosis outcomes, breast cancer women must subsequently deal with the various menopausal symptoms that are associated with a CIA-induced drop in estrogen level (such as cognitive function decline, physical and psychological symptoms, vasomotor symptoms, reproductive and sexual function problems, and body weight change). The present article describes the female menstrual cycle, the mechanism and risk factors of CIA, and the range of menopausal symptoms. Furthermore, we summarized methods of assessing menopausal symptoms and compared five common rating scales of menopausal symptoms. By better understanding the potential menopausal symptoms, researchers and clinicians may then select the most appropriate scale based on the situational needs in order to evaluate the severity of menopausal symptoms that are experienced by breast cancer women.