Anti-Müllerian hormone: determination of ovarian reserve in early breast cancer patients

Breast cancer is the most common invasive cancer in women of reproductive age. In young women, chemotherapy may induce amenorrhea: it is still uncertain how to assess menopausal status in these patients despite the importance of its definition for choosing appropriate endocrine treatment. In the development of sensitive biomarkers for fertility and ovarian reserve, anti-Müllerian hormone (AMH) is considered a promising marker of ovarian reserve. The clearest data regarding a clinical use of AMH are related to the measurement of the ovarian pool in women who undergo IVF: the available data, also in breast cancer patients, seem to suggest that AMH measurement, before gonadotropin administration, can be a useful marker for the prediction of women at risk for poor-response or no response to ovarian stimulation. The utility of AMH as a potential marker of chemotherapy-induced ovarian follicular depletion and an early plasma marker of chemotherapy-induced gonadal damage has been evaluated both in young women after treatment for cancer in childhood and in young survivors of hematological malignancies and solid tumors. Several studies have demonstrated a potential utility of AMH, inhibin, or follicle-stimulating factor as biomarkers predicting infertility risk in breast cancer patients, but the studies conducted so far are not conclusive. Further studies are needed in order to define the regimen-specific action of chemotherapy on AMH levels, the percentage of post-treatment recovery of plasma levels of the hormone, and the relationship between menopausal status and AMH.

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Burning Questions in the Oncofertility Counseling of Young Breast Cancer Patients

Breast Cancer Basic and Clinical Research ◽

10.1177/1178223420954179 ◽

2020 ◽

Vol 14 ◽

pp. 117822342095417 ◽

Cited By ~ 1

Author(s):

Luca Arecco ◽

Marta Perachino ◽

Alessandra Damassi ◽

Maria Maddalena Latocca ◽

Davide Soldato ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Fertility Preservation ◽

Young Women ◽

Reproductive Age ◽

Prior History ◽

Breast Cancer Patients ◽

History Of ◽

Anticancer Treatment ◽

Young Breast Cancer

The improved prognosis of breast cancer patients makes survivorship issues an area of crucial importance. In this regard, an increased attention is needed toward the development of potential anticancer treatment-related long-term side-effects, including gonadal failure and infertility in young women. Therefore, fertility preservation and family planning are crucial issues to be addressed in all young women of reproductive age with newly diagnosed cancer. Despite a growing availability of data on the efficacy and safety of fertility preservation options and the fact that conceiving after prior history of breast cancer has become more accepted over time, there are still several gray zones in this field so that many physicians remain uncomfortable to deal with these topics. The purpose of this review is to answer some of the most controversial questions frequently asked by patients during their oncofertility counseling, in order to provide a detailed and up-to-date overview on the evidence available in this field to physicians involved in the care of young women with breast cancer.

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MCM3 upregulation confers endocrine resistance in breast cancer and is a predictive marker of diminished tamoxifen benefit

npj Breast Cancer ◽

10.1038/s41523-020-00210-8 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Sanne Løkkegaard ◽

Daniel Elias ◽

Carla L. Alves ◽

Martin V. Bennetzen ◽

Anne-Vibeke Lænkholm ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Patients ◽

Endocrine Therapy ◽

Endocrine Resistance ◽

Predictive Marker ◽

Endocrine Treatment ◽

Breast Cancer Patients ◽

Minichromosome Maintenance ◽

Primary Tumors

AbstractResistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer is a major clinical problem with poorly understood mechanisms. There is an unmet need for prognostic and predictive biomarkers to allow appropriate therapeutic targeting. We evaluated the mechanism by which minichromosome maintenance protein 3 (MCM3) influences endocrine resistance and its predictive/prognostic potential in ER+ breast cancer. We discovered that ER+ breast cancer cells survive tamoxifen and letrozole treatments through upregulation of minichromosome maintenance proteins (MCMs), including MCM3, which are key molecules in the cell cycle and DNA replication. Lowering MCM3 expression in endocrine-resistant cells restored drug sensitivity and altered phosphorylation of cell cycle regulators, including p53(Ser315,33), CHK1(Ser317), and cdc25b(Ser323), suggesting that the interaction of MCM3 with cell cycle proteins is an important mechanism of overcoming replicative stress and anti-proliferative effects of endocrine treatments. Interestingly, the MCM3 levels did not affect the efficacy of growth inhibitory by CDK4/6 inhibitors. Evaluation of MCM3 levels in primary tumors from four independent cohorts of breast cancer patients receiving adjuvant tamoxifen mono-therapy or no adjuvant treatment, including the Stockholm tamoxifen (STO-3) trial, showed MCM3 to be an independent prognostic marker adding information beyond Ki67. In addition, MCM3 was shown to be a predictive marker of response to endocrine treatment. Our study reveals a coordinated signaling network centered around MCM3 that limits response to endocrine therapy in ER+ breast cancer and identifies MCM3 as a clinically useful prognostic and predictive biomarker that allows personalized treatment of ER+ breast cancer patients.

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141P Cognitive impairment among breast cancer patients receiving endocrine treatment: A comparative study between aromatase inhibitors and tamoxifen

Annals of Oncology ◽

10.1016/j.annonc.2021.03.155 ◽

2021 ◽

Vol 32 ◽

pp. S82

Author(s):

I. Ben Abdallah ◽

H. Rachdi ◽

N. Mejri ◽

Y. Berrazega ◽

H. El Benna ◽

...

Keyword(s):

Breast Cancer ◽

Cognitive Impairment ◽

Comparative Study ◽

Cancer Patients ◽

Aromatase Inhibitors ◽

Endocrine Treatment ◽

Breast Cancer Patients

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Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy

Cancers ◽

10.3390/cancers13040771 ◽

2021 ◽

Vol 13 (4) ◽

pp. 771

Author(s):

Tessa A. M. Mulder ◽

Mirjam de With ◽

Marzia del Re ◽

Romano Danesi ◽

Ron H. J. Mathijssen ◽

...

Keyword(s):

Breast Cancer ◽

Clinical Outcome ◽

Cancer Patients ◽

Plasma Concentrations ◽

Tamoxifen Treatment ◽

Current Status ◽

Endocrine Treatment ◽

Breast Cancer Patients ◽

Er Positive ◽

Positive Breast Cancer

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

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Serum levels of oxidative stress marker malondialdehyde in breast cancer patients in relation to pathohistological factors, estrogen receptors, menopausal status, and age

Journal of Health Sciences ◽

10.17532/jhsci.2018.263 ◽

2018 ◽

Vol 8 (3) ◽

pp. 154-161

Author(s):

Jasmina Gubaljevic ◽

Nahida Srabović ◽

Adlija Jevrić-Čaušević ◽

Adaleta Softić ◽

Adi Rifatbegović ◽

...

Keyword(s):

Breast Cancer ◽

Lymph Node ◽

Lymph Nodes ◽

Cancer Patients ◽

Benign Breast Disease ◽

Menopausal Status ◽

Serum Levels ◽

Breast Disease ◽

Breast Cancer Patients ◽

Node Metastases

Introduction: The aim of this study was to determine the serum levels of malondialdehyde (MDA) in patients with invasive breast cancer in relation to its serum levels in patients with benign breast disease, and to investigate correlation between MDA serum levels with pathohistological prognostic factors (tumor size, lymph node involvement, and histologic grade [HG]), estrogen receptor (ER) status, and with breast cancer patient’s age and menopausal status. Methods: A total of 43 with well-documented invasive breast cancer were included in this study: 27 with positive axillary’s lymph nodes, and 16 with negative axillary’s lymph nodes, and 39 patients with findings of benign breast diseases. MDA determination in serum of breast cancer and benign breast disease patients was performed by the fluorimetric method, immunohistochemical staining was performed for ER, and routine pathohistological examination was conducted for pathohistological factors. Results: MDA serum levels in breast cancer patients were significantly higher than MDA serum levels in benign breast disease patients (p = 0.042). No statistically significant difference between MDA serum levels in breast cancer patients with and without lymph node metastases was found (p = 0.238). No statistically significant correlations between MDA serum levels and tumor size (p = 0.256), HG (p = 0.124), or number of positive lymph nodes (0.113) were found. A statistically significant correlation between serum MDA levels and ages of breast cancer patients with lymph node metastases was found (p = 0.006). Conclusion: Obtained results support the importance of MDA in the carcinogenesis of breast cancer. According to our findings, serum level of MDA could not be a useful prognostic factor in breast cancer.

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Young Age is not an Ominous Prognostic Factor in Breast Cancer Patients

Tumori Journal ◽

10.1177/030089168707300305 ◽

1987 ◽

Vol 73 (3) ◽

pp. 233-235 ◽

Cited By ~ 15

Author(s):

Giuseppe Muscolino ◽

Corrado Villani ◽

Amedeo Vittorio Bedini ◽

Alberto Luini ◽

Bruno Salvadori

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Cancer Patients ◽

Young Women ◽

Survival Rates ◽

Disease Free Survival ◽

Young Age ◽

Breast Cancer Patients ◽

Free Survival ◽

Disease Free

Analysis of a series of 137 women 20–30 years of age, operated for breast carcinoma, excluding patients pregnant, lactating or with inflammatory cancer, showed that disease-free survival rates were similar and not lower than those reported for a large series of 716 breast cancer patients of all ages, treated and followed at the same Institute. Ten-year disease-free survival rates for the two series of 137 young women and 716 patients of all ages were 43.7% and 47.1% respectively. Even when considering the subgroups of patients with and without nodal axillary involvement, the corresponding figures for the two series considered were 72.6% vs. 72.1% (N−) and 25.1% vs. 24.5% (N+). It can be concluded that young age cannot be considered as an unfavorable prognostic factor.

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