Chemotherapy-induced Amenorrhea Research Articles

Abstract PO5-02-03: Does the recommendation of adjuvant CDK4/6 inhibitors implicate more ovarian suppression in premenopausal patients? A real-world study of a public and a private Argentinean institution

Abstract Introduction The recently published NATALEE trial has reported an increase of invasive disease free survival with the addition of ribociclib to hormone therapy during 3 years. Given the fact that aromatase inhibitors are required as the endocrine therapy backbone, premenopausal patients require ovarian function suppression (OFS) during CDKi treatment In the era of CDKi in the adjuvant setting, we hypothesize that the recommendation of GnRh analogs administration in addition to aromatase inhibitors will increase for premenopausal patients, given the inclusion criteria of this pivotal trial. For this reason, we explored in a retrospective cohort of a public and a private Argentinean institution to define whether the application of these criteria would imply an increase of the recommendation of OFS as part of the adjuvant endocrine treatment. Methods This was a multicentric retrospective cohort comprising premenopausal patients with early breast cancer diagnosis. Descriptive statistics were used to summarize data. The criteria for defining ribociclib recommendations were based on the phase III NATALEE clinical trial. Univariate analysis, including t and chi-square tests were used to determine differences between the populations that received and did not receive OFS, and between both participating institutions. p< 0,05 was considered to evaluate statistical significance. Results 191 premenopausal patients were incorporated in our analysis, and 48 (25.1%) received OFS. In this subgroup, mean age was lower (38.1 vs 44.2 years; p< 0.001) and the incidence of T3 (23.9 vs 6.5%; p=0.002), node-positive tumors (57.4 vs 28.9%; p=0.005), and prior chemotherapy treatment (75.5 vs 58.8%; p< 0.001) was higher. Among the 143 patients that did not receive OFS, 121 (84.6%) would have fulfilled clinical trial criteria for receiving ribociclib. No differences were observed according to the treating institution: 80.3 vs 87.8%; (p=0.22). The patient subgroup that would have met NATALEE criteria and did not receive OFS, had median age of 44.19 (SD 4.18), and had prior chemotherapy in 63.8% of the cases. Considering these characteristics, we observed that chemotherapy-induced amenorrhea and local institutional guidelines were the main explanations to understand why these moderate and high-risk patients did not receive OFS. Conclusion We observed that in premenopausal patients, the application of NATALEE criteria would result in an increase of the recommendation of GnRh analogues in around 80% of patients that had not received OFS in a retrospective cohort. This scenario may result in new challenges in treatment adherence and quality of life. In addition, this information is of special importance to carefully analyze the financial toxicity of a modern adjuvant approach that will be applied in a high proportion of eBC patients, especially in low and middle-income countries. Citation Format: Vanesa Lopez, Dana Narvaez, Jorge Nadal, Federico Waisberg, Adrian Nervo, Victoria Costanzo, Claudio Paletta, Fernando E. Petracci, Sergio Rivero, Alexis Ostinelli, Matías Chacón, Andrea Aguilar, Alejandro Kuzminin, Ageles Nico, Evelina Rovera, Naima Kassis, Maria Zapata Camaño, Carolina Almada, Maria Savignano, Gustavo Roganovich, Maria Eugenia Azar, Valeria Caceres. Does the recommendation of adjuvant CDK4/6 inhibitors implicate more ovarian suppression in premenopausal patients? A real-world study of a public and a private Argentinean institution [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 PO5-02-03.

Evaluation of Anti-Mullerian Hormone Levels, Antral Follicle Counts, and Mean Ovarian Volumes in Chemotherapy-Induced Amenorrhea among Breast Cancer Patients: A Prospective Clinical Study.

Estradiol (E2), a follicle-stimulating hormone (FSH), AMH, and inhibin B levels, along with AFC and MOV, are used to determine ovarian reserve in pre-menopausal women. Studies have shown that AMH levels are more sensitive than those of E2, FSH, and inhibin B and that AFC and MOV can be used to evaluate ovarian reserve. AMH, AFC, and MOV measurements were performed before and after adjuvant SC in 3-month periods for one year. Patients were classified as experiencing chemotherapy-induced amenorrhea (CIA) if they did not have menstrual cycles for a period of six months or longer following the conclusion of their chemotherapy treatment. We aimed to evaluate the factors affecting chemotherapy-induced amenorrhea in breast cancer patients treated with adjuvant chemotherapy and the performance of baseline measurements of AMH, AFC, and MOV to predict chemotherapy-induced amenorrhea. The effects of different chemotherapy regimens on the AMH level, AFC, and MOV in CIA patients were investigated. Seventy-one patients were eligible for this study, and the median age was 38 years (range: 23-45). The median follow-up was 37 months (range: 20-51), and CIA developed in 62% of the patients. The AMH level and AFC were significantly decreased one year after SC (p < 0.0001), whereas MOV was not (p = 0.507). AMH levels before chemotherapy (median: 1.520 vs. 0.755, p = 0.001) and at the end of the first year (median: 0.073 vs. 0.010, p = 0.030) and pre-treatment AFC (median: 12 vs. 4.50, p = 0.026) were lower in patients with CIA compared to those without CIA. The AMH levels before SC were the most valuable and earliest factor for predicting CIA development. In addition, there was no difference between the chemotherapy regimens (including or not including taxane) in terms of CIA development.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, β-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

Altered resting-state hippocampal functional connectivity in breast cancer survivors with chemotherapy-induced amenorrhea.

Amenorrhea induced decrease of hormones is associated with cognitive impairment. This study aimed to evaluate hippocampal functional connectivity patterns in chemotherapy-induced amenorrhea (CIA) breast cancer (BC) patients, to evaluate the relationship between the functional connectivity features and hormone levels. Neuropsychological test, functional magnetic resonance imaging, and assessment of hormone levels were conducted in 21 premenopausal BC patients before chemotherapy (t0 ) and 1 week after completing chemotherapy (t1 ). Twenty matched healthy controls (HC) were also included and underwent the same assessments at similar time intervals. Mixed effect analysis and paired t-test were used to compare differences in brain functional connectivity. Voxel-based paired t-tests revealed increased functional connectivity of the right and left hippocampus with the left fusiform gyrus, inferior and middle temporal gyrus, inferior occipital gyrus, left lingual gyrus, and parahippocampal gyrus after chemotherapy (p<.001) in CIA patients. Repeated measures analysis revealed significant group-by-time interactions in the left hippocampus with the bilateral fusiform gyrus, right parahippocampal gyrus, left inferior temporal gyrus, and left inferior occipital gyrus (p<.001). Premenopausal BC patients had no significant differences in cognitive function compared with HC at baseline. However, the CIA patients had high levels of self-rating depression scale, self-rating anxiety scale, total cholesterol, and triglycerides. Further, the CIA patients showed significant differences in hormone and fasting plasma glucose levels and cognitive performances between t0 and t1 (p<.05). Functional connectivity changes between the left hippocampus and the left inferior occipital gyrus was negatively correlated with E2 and luteinizing hormone changes (p<.05). The CIA patients had cognitive dysfunction mainly in memory and visual mobility. Chemotherapy may affect hippocampal-posterior cortical circuit which mediates visual processing in CIA patients. Moreover, E2 may be involved in this process.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Investigation of the female infertility risk associated with anti-cancer therapy.

Female infertility is a significant health issue worldwide with a rising incidence. Anti-cancer therapy is one of the most important reasons for increasing infertility. Although anti-cancer treatment increases the rate of survival, it decreases the quality of life through its side effects. The most substantial side effects are sexual dysfunction and infertility. Breast cancer is the most common cancer. The first-line treatment of breast cancer is chemotherapy by alkylating agents like cyclophosphamide, which leads to infertility. For instance, persistent chemotherapy-induced amenorrhea among breast cancer patients could affect almost half of the patients that undergo such therapy. However, some agents or therapeutic methods can ameliorate these intoxicating effects. Chemotherapy plus gonadotropin-releasing hormone agonist, in breast cancer patients, can not only improve overall survival but also reduce ovarian toxicity. Age plays an essential role in chemotherapy-induced amenorrhea. Chemotherapy at a younger age can reduce the risk of infertility. Gynecological cancers including uterine and ovarian cancer, which have high mortality rates, are the most related cancers to infertility. Surgery is the primary treatment of gynecological cancers. Studies demonstrated that fertility-sparing surgery is a better option than radical surgery. In addition, neoadjuvant chemotherapy is mostly a better option than primary cytoreductive surgery in terms of survival and fertility. Immune checkpoint inhibitors (ICIs) have recently played a major role in treating various cancer types. However, ICIs are associated with hypophysitis, which affects ovaries and can lead to infertility. There are some options for ovarian preservation such as embryo cryopreservation, oocyte cryopreservation, ovarian transposition, ovarian tissue cryopreservation, and ovarian suppression by GnRH agonists. Anti-müllerian hormone level can be utilized to monitor the ovarian reserve. Moreover, to avoid fertility loss, approaches such as using transplantation of human placenta mesenchymal stem cells, administrating anti-inflammatory agents and hormone therapy are under investigation.

Determining the Optimal Cut-Off Values of Serum E2 and FSH for Evaluating the Menopausal Status of Breast Cancer Patients in a Southern Chinese Population.

Background Chemotherapy-induced amenorrhea (CIA) is one of universal phenomena in breast cancer (BC) patients, and it causes difficulties in evaluating the actual menopausal status which is important for the oncologists to choose appropriate treatment. Currently, serum estradiol (E2) and follicle-stimulating hormone (FSH) levels are the most commonly used clinical parameters for the assessment of menopausal status in BC patients. However, the optimal cut-off points of serum E2 and FSH have little been explored in southern Chinese population. Objective This study is aimed to determine the optimal cut-off values of the serum E2 and FSH levels for evaluating the menopausal status of BC patients in a southern Chinese population. Methods A retrospective analysis was done among a total of 206 patients with BC from a southern Chinese area. The data of serum E2, FSH, and luteinizing hormone (LH) levels were collected and analyzed for the comparison purpose. The receiver-operating curve (ROC) was generated to assess the specificity and sensitivity of the three biomarkers in discriminating the menopausal status of BC patients. The optimal cut-off values were determined according to the Youden index and then compared with the recommended reference values by the Chinese Anti-cancer Association (CACA) and those recommended by the manufacturers. Results The areas under the ROC curves (AUCs) of E2, FSH, and LH were 0.846 (95% CI: 0.790-0.903), 0.781 (95% CI: 0.714-0.847) and 0.608 (95% CI: 0.526-0.690), respectively. The optimal cut-off values were 130.0 pg/mL for E2, 23.325 IU/L for FSH, and 11.625 IU/L for LH with a maximum of the Youden index. When E2, FSH, and LH were used in combination for ROC analysis, the AUC increased to 0.847 (95% CI: 0.790-0.904), which was higher than that of any other biomarker alone. In this study, the sensitivity and specificity of E2 and FSH were 91.6% and 73.70% and 94.4% and 58.6%, respectively, in comparison with 85.0% and 75.80% and 76.6% and 65.7% according to the CACA-recommended cut-off points, or 92.5% and 68.7% and 96.3% and 53.5% according to the manufacturer recommended cut-off points. Conclusion Considering the sensitivity and specificity of serum E2 and FSH for assessing the menopausal status, the optimal cut-off values determined in the present study were similar to the manufacturer's recommendations, but obviously superior to the cut-off points suggested by CACA. These cut-off points calculated in this study seem to be valuable in southern Chinese population and might be used by clinicians to make a correct medical decision for BC patients who would benefit from endocrine therapy of aromatase inhibitor (AI).

Ovarian function suppression is not indispensable in patients with early breast cancer who are older than age 40.

539 Background: Based on SOFT/TEXT studies, ovarian function suppression (OFS) has become the standard treatment for pre-menopausal breast cancer patients. However, a few studies reported more than 80% pre-menopausal breast cancer patients over 40 years old experienced permanent chemotherapy-induced amenorrhea (CIA) after chemotherapy, suggesting that these patients may not benefit from OFS. The purpose of this study was to evaluate the application value of OFS in early pre-menopausal hormonal receptor (HR)-positive breast cancer patients who experienced chemotherapy after 40 years old. Methods: 1386 pre-menopausal patients over 40 years of age with early HR-positive breast cancer underwent chemotherapy from 2010 to 2017 at the Sun Yat-Sen University Cancer Center. Serum hormone levels were used to define pre-menopausal status. OFS only referred to gonadotropin-releasing hormone agonist (GnRHa). Propensity score matching (PSM) was performed to reduce the selection bias between patients administrated with OFS and those without OFS. The prognostic value of OFS was determined using Kaplan-Meier and Cox proportional hazards analysis. Results: A total of 1386 patients (median age, 46 years; rang, 40-55 years) were enrolled in this study, 258 patients were treated with OFS and 1128 patients did not receive OFS treatment. After PSM, there were 258 patients allocated in Non-OFS group and 258 patients in OFS group. There had no statistically significant difference in terms of overall survival (OS) (p=0.5) and disease-free survival (DFS) (p=0.62) between Non-OFS group and OFS group. In Non-OFS group, 100 patients (8.86%) resumed menstruation after chemotherapy, and 1028 patients (91.14%) experienced permanent CIA. There also had no statistically significant difference in either OS (p=0.35) or DFS (p=0.79) between menstrual recovery group and permanent CIA group. In terms of the menstrual recovery duration time of the 100 patients who resumed menstruation, 37 patients (37%) were ≤ 6 months, 18 patients (18%) were 7 ̃ 12 months, and 45 patients (45%) were ＞ 12 months. In terms of the intervals from last time of chemotherapy to the beginning of menstrual recovery, 29 patients (29%) were ≤ 6 months, 16 patients (16%) were 7 ̃ 12 months, and 55 patients (55%) were ＞ 12 months. Finally, we analyzed the survival difference of different menstrual recovery durations and different intervals. We found that there still had no statistically significant difference in different recovery durations (OS, p=0.15; DFS, p=0.19) and different intervals (OS, p=0.11; DFS, p=0.24). Conclusions: In this study, early pre-menopausal HR-positive breast cancer patients who experienced chemotherapy after 40 years old did not benefit from OFS treatment in DFS and OS. These results suggest that OFS is not indispensable in early HR-positive breast cancer patients aged over 40 years.

Clinical characteristics, pregnancy outcomes and ovarian function of pregnancy-associated breast cancer patients: a retrospective age-matched study

BackgroundPregnancy-associated breast cancer (PABC) is a rare disease with increasing incidence. The prognosis, pregnancy outcomes and subsequent ovarian function of PABC patients are attracting attention.MethodsSixty-three PABC patients and 126 age-matched non-PABC patients were obtained in Tongji Hospital from January 2011 to September 2019. The clinical characteristics and ovarian function of PABC patients were compared with those of non-PABC patients. The pregnancy outcomes and neonatal outcomes of patients with breast cancer diagnosed during pregnancy (BCP) were described. Nonparametric tests, the χ2-test Kaplan–Meier, Cox regression and binomial logistic regression were used for analysis.ResultsPABC patients were diagnosed with a more advanced tumour stage (II: 47.6% vs. 45.2%, III: 33.3% vs. 19.8%, IV 3.2% vs. 0%, p = 0.003), which caused worse progression-free survival (PFS) (log-rank p = 0.0138) and breast cancer-specific survival (CSS) (log-rank p = 0.0076) than non-PABC patients. Tumour stage (III/IV vs. 0/I/II) (HR 16.017, 95% CI 5.830 ~ 44.006, p < 0.001) and endocrine therapy (HR 0.254, 95% CI 0.099 ~ 0.653, p = 0.004) were predictors of PFS. Tumour stage (III/IV vs. 0/I/II) (HR 30.875, 95% CI 7.232 ~ 131.820, p < 0.001), endocrine therapy (HR 0.200, 95% CI 0.049 ~ 0.818, p = 0.025) and targeted therapy (HR 0.143, 95% CI 0.028 ~ 0.743, p = 0.021) were predictors for breast CSS. Among the 15 BCP patients, 11 patients voluntarily continued their pregnancy, and the newborns had no obvious birth defects, either in 5 patients who received chemotherapy or in 6 patients who did not receive chemotherapy during pregnancy. Among the patients who received chemotherapy and did not receive endocrine therapy, 24 PABC patients and 48 non-PABC patients experienced chemotherapy-induced amenorrhea. There was no significant difference in resumption of menstruation between the two groups at 6 months and 12 months after the end of chemotherapy. No potential factors affecting resumption of menstruation were found.ConclusionPregnancy at diagnosis or within 1 year after delivery was not a risk factor for a worse prognosis in PABC patients. Compared with non-PABC patients, patients with PABC presented more aggressive tumour characteristics, which could mostly explain the worse prognosis observed in PABC patients. Receiving the appropriate regimen of chemotherapy in the second and third trimesters did not affect the maternal outcomes or neonatal outcomes of BCP patients. The special physiological state during pregnancy and lactation did not interfere with the damage of chemotherapy to ovarian function.

Effect of Menopausal Status on Chemotherapy-Induced Peripheral Neuropathy: Single-Institution Retrospective Audit

Abstract Introduction Paclitaxel can cause peripheral neuropathy in up to 60% of patients. Chemotherapy-induced peripheral neuropathy (CIPN) compromises quality of life and often leads to dose reduction or discontinuation of lifesaving chemotherapy. Preclinical models have suggested the possible neuroprotective effect of progesterone through remyelination and other mechanisms. Objectives The aim of this study was to evaluate the incidence of CIPN for different menopausal status. Materials and Methods We evaluated the effect of menopausal status, as a surrogate for circulating progesterone levels, on the risk of developing paclitaxel-induced peripheral neuropathy, in an audit of breast cancer patients. Data on CIPN (by clinical history and examination) and other variables were collected from the case charts of patients who had received paclitaxel-based chemotherapy for breast cancer at our institution. Results Five hundred and fifty women were treated with either neoadjuvant or adjuvant paclitaxel in this period. Of these, 262 (47.6%) women were premenopausal, 49 (8.9%) were perimenopausal, and 239 (43.5%) were postmenopausal at the time of diagnosis. Forty-five (8.1%) women had pre-existing diabetes mellitus. Two hundred and fifty-six (82.31%) developed chemotherapy-induced amenorrhea (CIA).CIPN was seen in 32.7% of women who continued to be premenopausal after receiving chemotherapy and 62.3% of postmenopausal women. Thirty-five (77.8%) out of forty-five diabetic women developed CIPN. On a multivariate logistic regression model, pre-existing diabetes mellitus (risk ratio [RR] = 2.64, 95% confidence interval [CI]: 1.26–5.52, p = 0.009), postmenopausal (RR = 2.84, 95% CI = 1.48–5.45, p = 0.002), and CIA status (RR = 2.17, 95% CI = 1.14–4.12, p = 0.018) were significantly associated with the development of CIPN. Number of cycles did not appear to have an impact (p= 0.819). Conclusions Postmenopausal status was independently associated with higher incidence of CIPN. One of the possible mechanisms could be lower circulating progesterone levels in these patients. A randomized controlled trial (CTRI/2015/11/006381) is ongoing to test this hypothesis.

Mobile web-based self-management program for breast cancer patients with chemotherapy-induced amenorrhoea: A quasi-experimental study.

AimThe aim of this study was to examine the effects of a mobile web‐based self‐management program on menopausal symptoms, self‐efficacy and quality of life in breast cancer patients with chemotherapy‐induced amenorrhoea.DesignA quasi‐experimental pretest–posttest design with repeated measures.MethodsThe study was carried out at a university medical centre between October 2017 and September 2018. The intervention group received a 12‐week mobile web‐based self‐management program including education and coaching/support. Multiple instruments were used to measure menopausal symptoms, self‐efficacy, and quality of life at pre‐test, after the intervention (post‐test), and 3 months post‐intervention (follow‐up test). Repeated measure ANOVA was used to analyse the data.ResultsIn the intervention group, menopausal symptoms were significantly improved compared to the control group at the follow‐up test. In the follow‐up test, the intervention group's self‐efficacy and quality of life were significantly improved, whereas that of the control group was decreased.

Age as an Independent Factor in the Permanent Chemotherapy-Induced Amenorrhea Incidence in Breast Cancer Patients at Dr. Moewardi Hospital, Surakarta, Indonesia

Background: Chemotherapy Induced Amenorrhea (CIA) is one common side effect of chemotherapy in breast cancer patients. Some who have CIA may experience menstruation return while others experience permanent CIA.&#x0D; Aim: to examines the factors that contribute to the incidence of persistent CIA in breast cancer patients.&#x0D; Methods: The population of this retrospective study was new breast cancer patients with premenopausal status when they started receiving chemotherapy at dr Moewardi Hospital Surakarta, Indonesia, from January 2019 to July 2021. To determine the relationship, the chi-square/Fisher’s exact test was performed. Risk factor analysis on the incidence of permanent CIA was carried out by using a bivariate logistic regression test, followed by multivariate analysis.&#x0D; Results: A number of 105 premenopausal breast cancer patients who received chemotherapy were found. Of these patients, 97 (93.38%) patients experienced CIA and 8 patients (6.62%) continued to menstruate. Of all the subjects having CIA, 49 patients (46.67%) menstruated again while the other 48 (45.71%) had persistent CIA. Age factor has a significant relationship with the incidence of permanent CIA (p =&lt; 0.001), where patients aged &gt; 45 years tend to have permanent CIA incidence with a proportion of 42 patients (87.5%) (p &lt; 0.05). The multivariate analysis showed that age &gt; 45 years (OR = 75.117; 95% CI = 12.671-445.311; p = &lt; 0.001) was the most dominant risk factor associated with the incidence of permanent CIA, while other variables as risk factors for permanent CIA based on multivariate analysis were Stage III (R = 6.677; 95% CI = 1.370-32,545; p = 0.019) compared to stages I and II, and BMI in the normal category (OR = 5.485; 95% CI = 1.083-27.786; p = 0.040) compared to excess BMI. The other variables were not found to be associated with the incidence of permanent CIA.&#x0D; Conclusion: Age is a major factor associated with permanent CIA incidence. Other factors related to this study are staging and BMI.&#x0D; &#x0D; Keywords: Age, Permanent, Chemotherapy Induced Amenorrhea, Breast Cancer

Amenorrhea in women with breast cancer who received chemotherapy: a case report

Introduction: Breast cancer is the second most common cancer in premenopause age, has a better outcome now. Increasing early detection rates and the effectiveness of adjuvant chemotherapy treatments are factors that influence the prognosis dan survival rate. However, adjuvant chemotherapy treatment can lead to ovarian dysfunction resulting in decreased quality of life.Case: A-29-year-old woman with breast cancer received a chemotherapy regimen of Docetaxel, Doxorubicin, and Cyclophosphamide for six cycles and had no menstrual bleeding (amenorrhoea) after chemotherapy finished. Physical examination, gynecology, and ultrasound showed no abnormalities. However, the Anti-Mullerian Hormone (AMH) immunoserology laboratory test showed shallow results.Conclusion: The gonad toxicity effects of chemotherapy on breast cancer can cause premature ovarian failure, which can manifest as oligomenorrhea, amenorrhea, or known as chemotherapy-induced amenorrhea (CIA), which can lead to induction of premature menopause or chemotherapy-induced menopause (CIM).

Chemotherapy-induced ovarian failure in young women with early breast cancer: Prospective analysis of four randomised neoadjuvant/adjuvant breast cancer trials

BackgroundYoung women receiving chemotherapy for early breast cancer (EBC) have a high probability for ovarian failure, defined by chemotherapy-induced amenorrhea (CIA) as a surrogate. CIA is insufficiently reliable and reproducible. We analysed chemotherapy-induced ovarian failure (CIOF) by assessing hormone parameters, CIA, and antral follicle count (AFC). MethodsBlood samples of women aged ≤45 years treated with anthracycline/taxane-based chemotherapy for EBC from four neoadjuvant/adjuvant trials were collected at baseline, at the end of treatment (EOT), and at 6, 12, 18, and 24 months after EOT. Centrally assessed oestradiol (cutoff <52.2 ng/L) and follicle-stimulating hormone (cutoff >12.4IU/L) were used to define CIOF for patients with baseline premenopausal hormone levels, anti-Müllerian hormone (AMH), and AFC to assess ovarian reserve. Further analyses included CIA, regain of premenopausal hormone levels, and disease-free survival (DFS) also in subgroups. ResultsSix hundred ninety-six patients aged ≤45 years had premenopausal hormone levels at baseline. Overall, 85.1% (592/696) experienced CIOF at EOT, and 147 of 592 had further hormone measurements after EOT. Of those, 32.7% (48/147) regained premenopausal hormone levels after 6 months, 57.9% (66/114) regained premenopausal hormone levels after 12 months, 83.0% (73/88) regained premenopausal hormone levels after 18 months, and 89.2% (74/83) regained premenopausal hormone levels after 24 months. After 24 months, 72.4% (21/29) of patients without CIOF and 100% (14/14) with CIOF had low AMH levels. Four-year DFS without CIOF versus CIOF was 65.9% versus 84.6% (hazard ratio [HR] = 2.09, 95% confidence interval [CI]: 1.37–3.19; P < 0.001); in hormone receptor positive 61.8% versus 87.5% (HR = 2.69, 95% CI: 1.57–4.60; P < 0.001); in <30 years 68.3% versus 92.6% (HR = 4.87, 95% CI: 1.05–22.63; P = 0.026). ConclusionMost premenopausal women experienced CIOF after chemotherapy for EBC. After 2 years, nearly all regain premenopausal hormone levels. CIOF was associated with better DFS, especially in patients with hormone receptor–positive EBC or aged <30 years.

Adjuvant Aromatase Inhibitors or Tamoxifen Following Chemotherapy for Perimenopausal Breast Cancer Patients.

BackgroundThe benefit of adjuvant aromatase inhibitors (AI) vs tamoxifen has been investigated in randomized clinical trials for premenopausal and postmenopausal patients with early, estrogen receptor–positive (ER+) breast cancer. The optimal endocrine treatment for chemotherapy-treated perimenopausal women, who generally develop chemotherapy-induced amenorrhea, is uncertain.MethodsAll Dutch women who received adjuvant chemotherapy and endocrine treatment for stage I-III, ER+ (>10% positive cells), invasive breast cancer diagnosed between 2004 and 2007 were identified through the Netherlands Cancer Registry. Included women were considered perimenopausal based on an age at diagnosis of 45 to 50 years (n = 2295). For each patient, AI treatment duration relative to total endocrine treatment duration was calculated. Predominantly tamoxifen-treated patients (AI < 25%) were compared with those receiving AI and tamoxifen for a similar duration (AI 25%-75%) and those mostly using AI (AI > 75%). Adjusted hazard ratios (HRs) for recurrence-free survival (RFS) and overall survival were calculated using time-dependent Cox regression.ResultsAfter an average follow-up of 7.6 years, 377 RFS events occurred. Women mostly receiving AI (AI > 75%) had the best RFS (adjusted HR = 0.63, 95% confidence interval = 0.46 to 0.86) followed by those receiving AI 25% to 75% (adjusted HR = 0.85, 95% confidence interval = 0.65 to 1.12) compared with predominantly tamoxifen-treated women. Trend analyses showed that every 10% increase in AI-endocrine treatment ratio reduced RFS event risk by 5% (2-sided Ptrend = .002). In total, 236 deaths occurred; hazard ratios for overall survival showed similar trends.ConclusionsThese results suggest that the best adjuvant endocrine treatment for chemotherapy-treated, ER+ breast cancer patients diagnosed aged 45-50 years consists of mainly AI followed by a switch strategy and mainly tamoxifen.

Chemotherapy-induced amenorrhea and its effects on fertility in long-term female survivors of classic osteosarcoma.

To explore the effect of chemotherapy-induced amenorrhea (CIA) on female osteosarcoma patients' fertility function, we investigated and analyzed their marital status, fertility, and menstrual status in a retrospective cohort study. We selected female osteosarcoma patients from database from January 2004 to December 2013. Patients' characteristics such as age, tumor location, marital status, menstrual status, and fertility status were collected. The data were analyzed using the Statistical Package for the Social Sciences (SPSS), version 22. A total of 122 female patients met these criteria and finally responded by questionnaire and telephone follow-up. The marriage rate of female osteosarcoma survivors was 50.8% (62/122), which was significantly lower than the control group (p = 0.000). The average marriage age of female osteosarcoma survivors was 25.5, which was obviously higher than the control group (p = 0.000). CIA occurred in 46 (36.1%) patients. We then found that the incidence of CIA was higher in older patients. (p = 0.011). All of the married patients wanted to have children, and 67.8% (42/62) of them had given birth after chemotherapy. The fertility of married patients with CIA was significantly reduced compared to that of married patients without CIA. (p = 0.001). The patients with CIA have higher risk of impaired reproductive function than those who did not. Fertility preservation option before the start of the chemotherapy is important. And it is much value to record menstrual pattern and detect sex steroid levels after 6months of therapy in order to be able to evaluate the fertility status.

Protective effect of goserelin on ovarian reserve during (neo)adjuvant chemotherapy in young breast cancer patients: a prospective cohort study in China.

Does goserelin, a GnRH agonist, have a protective effect in young breast cancer patients in terms of ovarian reserve markers anti-Müllerian hormone (AMH) and antral follicle count (AFC) during chemotherapy? Compared with chemotherapy alone, concurrent goserelin is associated with a higher probability of ovarian reserve recovery at 1 year after chemotherapy. Previous studies on the administration of goserelin to protect ovarian function during chemotherapy have produced conflicting results because of the endpoint used, namely, chemotherapy-induced amenorrhoea. Reproductive medicine specialists consider AMH and AFC as the most sensitive ovarian reserve markers; however, they have never been used as biomarkers to assess the potential protective effects on ovarian reserve of goserelin during chemotherapy. This was a prospective cohort study in which patients were assigned to receive (neo)adjuvant chemotherapy with goserelin (the goserelin group) or without goserelin (the control group) according to each patient's preference. Of 242 breast cancer patients enrolled between December 2015 and November 2019, 76 in control group and 73 in goserelin group were able to be assessed at 1 year after chemotherapy. Premenopausal patients with a regular menstrual cycle and aged 18-45 years were eligible for enrolment if they were newly diagnosed with stages I-III breast cancer for which treatment with adjuvant or neoadjuvant chemotherapy was planned. Each patient in the goserelin group was given a subcutaneous dose of 3.6 mg at least 1 week before the first cycle of chemotherapy and then every 4 weeks for the duration of chemotherapy. Ovarian reserve markers and menstrual status were evaluated before and after chemotherapy in the two treatment groups. The primary endpoint was the AMH recovery rate, the secondary endpoints were the recovery rates of AFC, estradiol (E2), follicle-stimulating hormone (FSH) and menstruation. Among 149 patients (76 in the control group and 73 in the goserelin group) with complete data at 1 year after chemotherapy, the adjusted recovery rate of AMH was 46.5% and 21.8% in the goserelin group and control group, respectively (odds ratio: 3.08; P = 0.002). The trends in AFC and FSH recovery rates were consistent with that in AMH recovery rate. Notably, AMH levels remained low in 41.3% of patients whose menstrual activity had resumed. Randomisation was not performed because of ethical considerations, so selection bias was inevitable, although propensity score weighting was done. The study was also underpowered because 21.5% (52/242) of enrolled patients received GnRH agonist-containing endocrine therapy and could not be analysed at 1 and 2 years after chemotherapy. Our results indicate that co-administration of goserelin with chemotherapy provides obvious ovarian reserve protection in these young breast cancer patients. We expect that these results will be applicable in clinical practice for young breast cancer patients. This study was funded by the National Key R&D Program of China No. 2016YFC0901302, by the Research and Development Fund of Peking University People's Hospital No. RD2014-13, RDY2017-19 and by AstraZeneca. The authors have no disclosures. NCT02430103.

Antimullerian Hormone as a Serum Biomarker for Risk of Chemotherapy-Induced Amenorrhea.

Antimullerian hormone (AMH) is a promising biomarker for ovarian reserve. In this study, we assessed AMH before and 1 year after initiation of adjuvant chemotherapy onNational Surgical Adjuvant Breast and Bowel Project (NSABP)/NRG Oncology B-47 in female participants aged 42 years and younger (median age = 39 years). At baseline, median AMH was 1.2 ng/mL; 13 (4.7%) values were less than 0.1 ng/mL (the threshold for detectable levels, in the perimenopause and menopause range), and 57 values (20.6%) were less than 0.5 ng/mL. At 1 year, 215 (77.6%) were less than 0.1 ng/mL, and 264 (95.3%) were less than 0.5 ng/mL. Postchemotherapy menses were reported by 46.2% of participants. Multivariable logistic regression found that the odds of having postchemotherapy menses increased with younger age, higher body mass index, and higher prechemotherapy AMH, but not by trastuzumab administration or by the choice of chemotherapy (doxorubicin-cyclophosphamide followed by paclitaxel vs docetaxel-cyclophosphamide). We conclude that higher prechemotherapy AMH predicts a lower risk of chemotherapy-induced amenorrhea and that AMH 1 year after chemotherapy initiation is not informative in this setting because it is likely to be very low.

Prevalence and Potential Factors Related to Irreversible Chemotherapy-Induced Amenorrhea in Premenopausal Breast Cancer Patients

Objective: To evaluate the prevalence and potential factors related to irreversible chemotherapy-induced amenorrhea (CIA) in premenopausal women with breast cancer. Methods: First diagnosis breast cancer women in Stages I-III who had menstruation within three months before receiving chemotherapy and completed a course of treatment were interviewed about the menstrual cycle after a complete course of chemotherapy and the subsequent menstrual status. Clinical data were retrospectively reviewed. Age at starting chemotherapy was calculated for an optimal cut-off point by using the receiver operating characteristic curve to predict irreversible CIA. The clinicopathological variables were compared using univariate and multivariate analysis to identify the independent factors related to irreversible CIA. Results: One hundred and fifty-four premenopausal breast cancer women who met the inclusion criteria were interviewed. They were treated with chemotherapy between October 1999 and September 2018. The median age at the start of treatment was 43.5 years. One hundred forty-two patients (92.2%) developed CIA and 37 cases subsequently resumed menstruation (RM). Thus, the prevalence of irreversible CIA was 68.2%. The group &gt; 45 years of age, estrogen receptor-positive, progesterone receptor-positive and maintenance treatment with tamoxifen significantly developed irreversible CIA in univariate analysis. However, only the &gt; 45-year-old group was an independent factor for the CIA with an adjusted odds ratio of 23.04. Conclusion: Nearly 70% of premenopausal breast cancer women developed irreversible CIA and the independent factor for this event was being older than 45-years-old when receiving chemotherapy.

L’insuffisance ovarienne chimio-induite dans le cancer du sein : étude rétrospective de 100 cas

Breast cancers affect about a quarter of women of reproductive age worldwide. Chemotherapy is frequently indicated due to the aggressive biomolecular cancer subtypes usually observed in the localized forms, which may compromise the fertility of these young patients. The aim of our study is to report the incidence of chemotherapy induced ovarian failure in premenopausal breast cancer patients after chemotherapy, and to identify related risk factors. It is a retrospective cross-sectional cohort study which included all premenopausal patients with early breast cancer treated at the department of medical oncology, Hassan II University Hospital of Fez, during a period of one year. Chemotherapy induced amenorrhea (CIA) and associated risk factors were studied. The study included 100 patients. The mean age of the subjects was 36 years. The incidence of CIA was 82%, 66.7% regained menstruations. Risk factors associated with CIA were analyzed, only the patient age at diagnosis was found to be statistically significantly associated with CIA. Our study found a high incidence of CIOF (Chemotherapy-induced ovarian failure) with a relatively low incidence of reversible amenorrhea. Only the patient age has been shown to be an independent factor, statistically significantly associated with ovarian failure after chemotherapy. Methods of fertility preservation should be considered in those patients to reduce the impact of chemotherapy on ovarian reserves.