Evaluation of Primary and Recurrent Breast Cancer after Giving Adjuvant Therapy in Correlation with the Receptor Status.

Breast cancer is the most common type of cancer among women. The molecular subtypes of breast cancer, depending on the Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (HER-2) status, usually play a vital role for the adjuvant treatment. Interestingly, there is a good possibility of change of receptor status in the recurrence of same primary tumor. The study is designed April 2018 to March 2019 to see the concordance in triple-receptor expression (ER, PR, and HER-2) between the primary and the locally recurrent breast cancer patient and the results can be able to influence the management and prognosis of the breast cancer patients. This observational study was carried out in the department of surgical oncology, NICRH where total 48 patients were studied who were subjected to core biopsy of recurrent lesion for ER, PR and HER-2 status. A structured case record form was used to interview and collect data. Data analysis was done using SPSS version 26.0 to see concordance and discordance in triple-receptor expression between the primary and the locally recurrent breast cancer patient. Among 48 cases, 12(25.0%), 10(20.83%) and 2(4.16%) patients showed Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (Her-2) discordance that are statistically significant in every receptor status. Majority discordance of ER, PR and Her-2 were associated with invasive duct cell carcinoma (IDC); ER & Her-2 discordance was equally associated with histological grade 2 and 3 whereas PR discordance had significant association with grade 3. Staging of disease showed that all ER, PR and Her-2 discordance were associated with stage (p<0.05). Besides, majority discordance was mostly associated with lumpectomy except Her-2 discordance. Besides, among the adjuvant treatment regimen chemotherapy along with radiotherapy was mostly associated with discordance of all receptors (p<0.05). Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor (HER-2) status of primary breast cancer showed 25.0%, 20.83% and 4.16% discordant in recurrent episodes in this study. Invasive duct cell carcinoma, histological grade 2 and 3, stage II, stage III, MRM and CT along with RT are major attributable factors in this study.

Molecular Subtypes of Breast Cancer in a Tertiary Centre in Edo State: South-South Nigeria.

BACKGROUND: Breast cancer constitutes a significant public health issue in most resource-constrained nations due to its high morbidity and mortality rates. There is a paucity of knowledge of the molecular subtypes of breast cancer in Nigeria primarily due to the lack of immunohistochemistry. This study aims to identify the molecular subtypes of histologically confirmed breast cancer cases at the University of Benin Teaching Hospital, Benin City, Nigeria, using ER, PR and HER2/neu as immunohistochemical biomarkers. MATERIALS AND METHOD: Breast cancer specimens received in the Histopathology department of the University of Benin Teaching Hospital between 2019 and 2021 were used for this study. Representative sections of paraffin-embedded blocks were recut for histological typing, tumour grading, and immunohistochemistry. RESULTS: A total of 330 cases were evaluated in this study. The average age was 49 years, with a M:F of 40.3:1. The most frequent histological type was invasive breast cancer (92.1%). Two hundred and forty-two (73.3%) cases were categorized as grade II tumours. The steroid hormone receptor positivity was 39.4%. Oestrogen and Progesterone receptor positivity were 39.4% and 22.1%, respectively. HER2/neu was positive in 16.4% of the cases. Triple-negative breast cancer (TNBC) was the most common molecular subtype, accounting for 49.4% of cases. Luminal A, Luminal B, and HER2/neu enriched subtypes were each found in 34.2%, 5.2%, and 11.2% of cases, respectively. CONCLUSION: Triple-negative breast cancers predominated among the study population and were more common in high-grade tumours with unfavourable histological types and among women who were younger than their Caucasian counterparts.

CONTEXTE: Le cancer du sein constitue un problème de santé publique majeur dans la plupart des nations aux ressources limitées en raison de son taux élevé de morbidité et de mortalité. Il existe une pénurie de connaissances sur les sous-types moléculaires du cancer du sein au Nigeria, principalement en raison du manque d'immunohistochimie. Cette étude vise à identifier les sous-types moléculaires des cas de cancer du sein confirmés histologiquement à l'Hôpital Universitaire de Benin, Benin City, Nigeria, en utilisant les biomarqueurs immunohistochimiques ER, PR et HER2/neu. MATÉRIAUX ET MÉTHODE: Les échantillons de cancer du sein reçus dans le département d'histopathologie de l'Hôpital Universitaire de Benin entre 2019 et 2021 ont été utilisés pour cette étude. Des sections représentatives de blocs inclus en paraffine ont été recoupées pour le typage histologique, le classement des tumeurs et l'immunohistochimie. RÉSULTATS: Un total de 330 cas ont été évalués dans cette étude. L'âge moyen était de 49 ans, avec un rapport H de 40,3:1. Le type histologique le plus fréquent était le cancer du sein invasif (92,1 %). Deux cent quarante-deux (73,3 %) cas ont été classés comme des tumeurs de grade II. La positivité des récepteurs hormonaux stéroïdiens était de 39,4 %. Les récepteurs des œstrogènes et de la progestérone étaient positifs dans 39,4 % et 22,1 % des cas, respectivement. HER2/neu était positif dans 16,4 % des cas. Le cancer du sein triple négatif (CSTN) était le sous-type moléculaire le plus courant, représentant 49,4 % des cas. Les sous-types Luminal A, Luminal B et enrichi en HER2/neu ont été trouvés dans 34,2 %, 5,2 % et 11,2 % des cas, respectivement. CONCLUSION: Les cancers du sein triple négatif prédominaient parmi la population étudiée et étaient plus fréquents dans les tumeurs de haut grade avec des types histologiques défavorables et chez les femmes plus jeunes que leurs homologues caucasiennes.

Trends in the incidence and survival of women with hormone receptor-positive breast cancer from 1990 to 2019: a large population-based analysis.

Hormone receptor-positive breast cancer (BC) is the most prevalent subtype of BC and is generally correlated with a favorable prognosis. This study aimed to determine the incidence and survival trends among women diagnosed with hormone receptor-positive BC between 1990 and 2019. Female patients with hormone receptor-positive BC for calendar years 1990-2019 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database and categorized into six diagnostic groups according to the year of diagnosis. Age-adjusted incidence rates (IRs) were calculated using joinpoint regression. We used the Kaplan-Meier method and multivariate Cox regression analyses to determine the association between diagnostic groups, and overall survival (OS) and BC-specific survival (BCSS). The final analysis included 370,729 women, among whom 37,943 (10.2%), 49,266 (13.3%), 55,652 (15.0%), 64,451 (17.4%), 77,127 (20.8%), and 86,290 (23.3%) were diagnosed between 1990 and 1994, 1995-1999, 2000-2004, 2005-2009, 2010-2014, and 2015-2019, respectively. Within the overall cohort, IRs gradually increased from 70 per 100,000 in 1990 to 113 per 100,000 in 2019 (average annual percent change, 1.59%; 95% CI, 1.18-1.99). Multivariate Cox regression analysis revealed that the survival outcomes gradually improved over nearly three decades among hormone receptor-positive BC patients, with a 0.8% and 1.3% decrease in risk for all-cause and BC-specific mortality each year, respectively. Compared to 1990-1994, hormone receptor-positive BC patients diagnosed in 2015-2019 had a 22% lower risk of all-cause death (hazard ratio [HR], 0.78; 95% CI, 0.76-0.81) and a 27% lower risk of BC-specific death (HR, 0.73; 95% CI, 0.70-0.76). The development of treatment strategies within the past three decades, especially endocrine therapy, may contribute to the continuous improvement of clinical outcomes in patients with hormone receptor-positive BC.

Neoadjuvant sunitinib plus exemestane in post-menopausal women with hormone receptor-positive/HER2-negative early-stage breast cancer (SUT_EXE-08): a phase I/II trial.

Neoadjuvant endocrine therapy (NET) for hormone receptor-positive (HR+) breast cancer might be as effective as chemotherapy, with a better toxicity profile. Blocking a crucial process such as angiogenesis with sunitinib may have a synergistic effect with NET. We aimed to assess the efficacy and safety of neoadjuvant sunitinib plus exemestane in early-stage HR+/HER2-negative breast cancer. In this phase I/II study, postmenopausal women with HR+/HER2- stage II-III breast cancer received neoadjuvant exemestane at conventional dose of 25mg plus sunitinib in a 3 + 3 design at 25mg (3/1weeks scheme) or 37.5mg continuous dose, for 6 months. Coprimary endpoints were the recommended dose of sunitinib combined with exemestane and objective response. Secondary endpoints included safety and biomarkers of early response. For 15 months, 18 patients were enrolled, 15 at sunitinib 25mg and 3 at 37.5mg. Median age was 73, 77% of patients had T2 tumors and 67% node-positive disease. The most common grade 2 toxicity was asthenia (44%), as was hypertension (22%) for grade 3. No grade 4-5 were reported. Twelve patients (66%) achieved an objective response. VEGFR-2 levels significantly decreased after one month of treatment. Differential gene expression analysis showed downregulation of ESR1, PGR and NAT1 in post-treatment samples and upregulation of EGFR, MYC, SFRP1, and FOXC1. PAM50 analysis on 83% of patients showed a prevalence of luminal A subtype, both in pre-treatment (63.6%) and post-treatment tumors (54.5%). Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer.Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009.

The Possible Role of Progesterone Receptors in Prostate Cancer Incidences in the Iraqi Population.

BACKGROUND: Prostate cancer (PCa) is one of the leading diseases causing mortality. It comes in the third rank of common cancer types. It is considered extremely a complicated cancer type since it occurs in highly steroid-responsive and dependent tissues. Many factors are considered to play an important role in the disease progression of PCa, with some functioning at the molecular level. METHODOLOGY: After applying the exclusion criteria, 200 patients who underwent proctectomy were included in this study. Following receiving patient consent, blood samples were withdrawn from patients, DNA was extracted, and precise polymerase chain reaction (PCR) amplification was conducted using specifically designed primers. The resulting amplicons were sequenced and analyzed. RESULTS: The progesterone receptor B (PGRB) DNA from patients showed four distinctive single-nucleotide polymorphisms (SNPs) at sites 11:101128812, 11:101128924, 11:101128949, and 11:101128986, which altered the amino acid sequences to Y>N, A>D, T>I, and C>R, respectively, compared to control. These SNPs resided in sensitive sites that either affected the control elements or promoted alterations in the protein configuration. This DNA change diminished the PGR gene function and promoted an imbalance in the encoded PGR protein structure and expression. CONCLUSIONS: Many factors may play a role in PCa manifestation, with steroids and progesterone initially noted as factors. Many studies have dealt with the hormonal effect on PCa; however, few have ultimately determined the molecular impact on disease progression. The presence of pathogenic SNPs in the enhancing region of the gene may impact the expression level of PGR. High or low expression levels may negatively affect gene function, which can be considered a reliable factor in prostate tumorigenesis.

Navigating precision: the crucial role of next-generation sequencing recurrence risk assessment in tailoring adjuvant therapy for hormone receptor-positive, human epidermal growth factor Receptor2-negative early breast cancer.

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common subtype, representing over two-thirds of new diagnoses. Adjuvant therapy, which encompasses various medications and treatment durations, is the standard approach for managing early stage HR+ HER2- breast cancer. Optimizing treatment is essential to minimize unnecessary side effects while addressing the biological variability inherent in HR+/HER2- breast cancers. Incorporating biological biomarkers into treatment decisions, alongside traditional clinical factors, is vital. Gene expression assays can identify patients unlikely to benefit from adjuvant chemotherapy, thereby refining treatment strategies and improving risk assessment. This paper reviews evidence for several genomic tests, including Oncotype DX, MammaPrint, Breast Cancer Index, RucurIndex, and EndoPredict, which assist in tailoring adjuvant therapy. Additionally, we explore the role of liquid biopsies in personalizing treatment, emphasizing the importance of considering late relapse risks and potential benefits of extended systemic therapy for HR+/HER2- breast cancer patients.

Supraphysiological Dose of Testosterone Impairs the Expression and Distribution of Sex Steroid Receptors during Endometrial Receptivity Development in Female Sprague-Dawley Rats.

This study aims to investigate the effect of a supraphysiological dose of testosterone on the levels of sex steroid hormones and the expression and distribution of sex steroid receptors in the uterus during the endometrial receptivity development period. In this study, adult female Sprague-Dawley rats (n = 24) were subcutaneously administered 1 mg/kg/day of testosterone alone or in combination with the inhibitors (finasteride or anastrozole or both) from day 1 to day 3 post-coitus, while a group of six untreated rats served as a control group. The rats were sacrificed on the evening of post-coital day 4 of to measure sex steroid hormone levels by ELISA. Meanwhile, gene expression and protein distribution of sex steroid receptors were analysed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), respectively. In this study, treatment with a supraphysiological dose of testosterone led to a significant reduction in oestrogen and progesterone levels compared to the control. The mRNA expression of the androgen receptor increased significantly in all treatment groups, while the mRNA expression of both the progesterone receptor and the oestrogen receptor-α decreased significantly in all treatment groups. The IHC findings of all sex steroid receptors were coherent with all mRNAs involved. This study shows that a supraphysiological dose of testosterone was able to interrupt the short period of the implantation window. This finding could serve as a basis for understanding the role of testosterone in endometrial receptivity in order to develop further therapeutic approaches targeting androgen-mediated disorders of endometrial receptivity.

Androgen receptor expression and clinical characteristics in breast cancer.

OBJECTIVE: To investigate the relationship between the expression of androgen receptor (AR) and clinical characteristics in breast cancer. PATIENTS AND METHODS: The clinical records of all 432 patients tested for AR in our institution between January 2020 and May 2023 were reviewed. Clinical characteristics, age, menopausal status, tumor node metastasis (TNM) stage, distant metastasis, pathological complete response (pCR), histopathological features histological grade, estrogen receptor (ER), progesterone receptor, Her-2, Ki-67, and molecular subtype were registered for all patients. RESULTS: About 377 (87.27%) of the 432 patients had AR expression. No significant difference in AR expression was found with age, menopausal status, TNM stage of primary tumor, or pCR. AR was positively and significantly associated with the histological grade, and recurrence. The AR expression was significantly related with molecular subtypes, including ER, PR Her-2, Ki67 and molecular subtype. ER (OR = 10.489, 95%CI: 5.470-21.569), PR (OR = 7.690, 95%CI: 3.974-16.129, Her-2 (OR = 10.489, 95%CI: 2.779-23.490 and tumor recurrence (OR = 0.110, 95%CI: 0.031-0.377 were significant independent risk factors affecting AR expression. CONCLUSIONS: AR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer.

Association of CYP7B1 expression with the prognosis of endometrial cancer: a retrospective study.

BACKGROUND: Endometrial cancer (EC) tissues express CYP7B1, but its association with prognosis needs to be investigated. METHODS: Immunohistochemistry and image analysis software were used to assess CYP7B1 protein expression in paraffin-embedded endometrial tumor sections. Associations between CYP7B1 and clinical factors were tested with the Wilcoxon rank-sum test. Kaplan-Meier curves were employed to describe survival, and differences were assessed using the log-rank test. Cox regression analysis was used to assess the association between CYP7B1 expression and the prognosis of patients with EC. RESULTS: A total of 307 patients were enrolled with an average age of 52.6 ± 8.0 years at diagnosis. During the period of follow-up, 46 patients (15.0%) died, and 29 (9.4%) suffered recurrence. The expression of CYP7B1 protein is significantly higher in the cytoplasm than in the nucleus (P < 0.001). Patients aged < 55 years (P = 0.040), ER-positive patients (P = 0.028) and PR-positive patients (P < 0.001) report higher levels of CYP7B1 protein. Both univariate (HR = 0.41, 95% CI: 0.18-0.90, P = 0.025) and multivariate (HR = 0.35, 95%CI:0.16-0.79, P = 0.011) Cox regression analyses demonstrate that high CYP7B1 protein expression predicts longer overall survival (OS). When considering only ER-positive patients (n = 265), CYP7B1 protein expression is more strongly associated with OS (HR = 0.20,95%CI:0.08-0.52, P = 0.001). The 3-year OS and 5-year OS in the low-CYP7B1 subgroup are 81.6% and 76.8%, respectively; while in the high-CYP7B1 subgroup are 93.0% and 92.0%, respectively (P = 0.021). CONCLUSIONS: High CYP7B1 protein expression predicted longer OS, suggesting that it may serve as an important molecular marker for EC prognosis.

Progesterone receptor B over progesterone receptor A prevents recurrence in bilateral endometriomas.

OBJECTIVE: Endometriosis is a disease in which stromal cells and endometrial glands extend outside of the uterine cavity. Nevertheless, treatment failure and recurrence cause difficulties in management. This study aimed to evaluate the receptor-level components of bilateral endometriomas in the recurrence state. METHODS: Our retrospective cohort study was conducted with patients who underwent surgery for bilateral endometriomas between 2015 and 2021. In total, 113 patients were allocated. A total of 76 patients did not meet the eligibility criteria, and the data of 37 patients were evaluated. Medical treatments, recurrences, and postoperative follow-up data were collected. In archived tissue samples, measurements of progesterone receptor A and progesterone receptor B, histoscores and immunoreactivity scores, and their ratios were calculated in the group that received no postoperative medical treatment. Criteria for recurrence were a repeat operation and/or the detection of a new endometrioma>2 cm at the follow-up examination. RESULTS: No recurrence was observed in 73.0% (n=27) of the cases, whereas recurrence was observed in 27.0% (n=10) of the participants. Patients without recurrence had significantly higher progesterone receptor B histoscore/progesterone receptor A histoscore and progesterone receptor B immunoreactivity score/progesterone receptor A immunoreactivity score results (p=0.01). Nevertheless, when the histoscores and immunoreactivity scores for both receptors were contrasted separately, there was no appreciable difference between them. CONCLUSION: The dominance of progesterone receptor B over progesterone receptor A was inversely proportional to the recurrence status in bilateral endometriomas. Furthermore, our study revealed that assessing receptor levels alone did not result in a significant difference in recurrence.

Clinicopathological characteristics and survival analysis of different molecular subtypes of breast invasive ductal carcinoma achieving pathological complete response through neoadjuvant chemotherapy.

BACKGROUND: To investigate the prognostic differences following the achievement of a pathological complete response (pCR) through neoadjuvant chemotherapy across different molecular subtypes of breast invasive ductal carcinoma. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) were identified for patients undergoing neoadjuvant chemotherapy who achieved pathological complete response for invasive ductal carcinoma of the breast between 2010 and 2019.Comparing the clinicopathological characteristics of patients across different molecular subtypes. Univariate and Cox multivariate analyses were utilized to identify independent predictors of overall survival (OS) and cancer-specific survival (CSS). The Kaplan-Meier method is used to compare OS and CSS among different molecular subtypes. After propensity score matching, subgroup analysis results were presented through forest plots. RESULTS: This study included 9,380 patients diagnosed with invasive ductal carcinoma, who were categorized into four molecular subtypes: 2,721 (29.01%) HR + /HER-2 + , 1,661 (17.71%) HR + /HER2-, 2,082 (22.20%) HR-/HER2 + , and 2,916 (31.08%) HR-/HER-2-. HR + /HER-2- subgroup exhibited a significantly higher proportion of patients under 50 years old than the other subtype groups (54.67% vs 40.2%, 50.35% and 51.82%, p < 0.01), and had a higher N2 + N3 stage (11.2% vs 7.24%, 8.69% and 7.48%, p < 0.01). Univariate and multivariate analysis revealed that molecular subtype was the independent risk factor for OS and CSS in patients(p < 0.05). The Kaplan-Meier curves indicated that the HR + /HER-2 + subtype had the highest OS and CSS(p < 0.05). Next, were the HR-/HER-2 + and HR-/HER-2- subtypes, with the HR + /HER-2- group having the lowest OS and CSS(p < 0.05). After propensity score matching, the OS and CSS of patients in the HR + /HER-2 + group remained higher compared to HR + /HER-2- group(p < 0.05). CONCLUSIONS: Patients with invasive ductal carcinoma of different molecular subtypes exhibit varying prognoses after achieving pCR to neoadjuvant chemotherapy. Those in the HR + /HER-2- group are younger, have a higher lymph node stage, and the lowest OS and CSS, whereas patients in the HR + /HER-2 + group have the highest OS and CSS.

Efficacy and safety of different regimens of neoadjuvant therapy in patients with hormone receptor-positive, her2-negative breast cancer: a network meta-analysis.

Introduction: The objective of this systematic review and network meta-analysis (NMA) is to assess the effectiveness and safety of various neoadjuvant treatment protocols in individuals diagnosed with hormone receptor-positive, her2 negative(HR+/HER2-) breast cancer. Materials and methods: A systematic search was conducted in four databases (Medline, Embase, Web of Science, and CENTRAL) from the inception of the databases to January 16, 2024, to identify randomized controlled trials (RCTs) to various neoadjuvant therapy options in patients diagnosed with hormone receptor-positive, HER2-negative breast cancer. A network meta-analysis was conducted to evaluate pathological complete response (pCR). Results: There were 17 randomized controlled trials (RCTs) included in the analysis. These trials examined 16 different treatment regimens and involved a total of 5752 participants. The analysis revealed that the six most effective neoadjuvant treatment regimens for HR+/HER2- breast cancer were: CT(A)+olaparib (82.5%), CT(A)+nivolumab (76.5%), Com (74.9%), CT (72.1%), Mono+eribulin (72.0%), and CT(A)+pembrolizumab (70.4%).Paired meta-analysis for pathological complete response (pCR) found no statistically significant distinction between treatment regimens that included both anthracycline and immunosuppressants and regimens that relied solely on anthracycline chemotherapy(OR:1.14, 95%ci 0.79-1.64, I2 = 71%, P=0.50). Similarly, there was no significant difference between platinum-based chemotherapy and anthracycline-basedchemotherapy(OR:1.37, 95%ci 0.53- 3.56, I2 = 11%, P=0.52). With regards to safety, adverse effects of grade 3-5 were observed, which included haematological toxicity, gastrointestinal reactions, skin and mucous membrane reactions, neuropathy, hepatotoxicity, and cardiac disorders. Conclusions: The CT(A)+Olaparib and CT(A)+nivolumab groups demonstrated superior efficacy in neoadjuvant therapy for HR+/HER2- breast cancer. Furthermore, it is crucial to focus on effectively managing the adverse effects of the treatment plan to enhance patient's ability to tolerate it. Given the constraints of the current research, additional well-executed and suitable RCTs are necessary to validate the findings of this investigation. Although pCR is valuable in assessing the effect of neoadjuvant therapy in some cases, prognostic prediction and efficacy assessment in patients with HR+/HER2- breast cancer should be based on a combination of broader clinical and biological characteristics. Systematic review registration: PROSPERO https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024534539, CRD42024501740.

Deletion of Nuclear Progesterone Receptors From Kisspeptin Cells Does Not Impair Negative Feedback in Female Mice.

Reproductive function in mammals depends on the ability of progesterone (P4) to suppress pulsatile gonadotrophin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion in a homeostatic-negative feedback loop. Previous research identified that cells upstream from GnRH neurons expressing the nuclear progesterone receptor (PGR) are required for P4-negative feedback. However, the identity of these cells and the mechanism by which they reduce GnRH/LH pulsatile secretion is unknown. We aimed to address the hypothesis that PGR expressed by a neural population in the arcuate nucleus recently identified as the GnRH pulse generator, cells expressing kisspeptin, neurokinin B, and dynorphin (KNDy cells), mediate P4-negative feedback. To achieve this, we used female mice with the PGR gene conditionally deleted from kisspeptin cells (KPRKO mice) and observed a substantial decrease in the percentage of KNDy neurons coexpressing PGR messenger RNA (mRNA) (11% in KPRKO mice vs 86% in wild-type [WT] mice). However, KPRKO mice did not display changes in the frequency or amplitude of LH pulses in diestrus or estrus, nor in the ability of exogenous P4 to blunt a postcastration increase in LH. Further, mRNA expression of arcuate kisspeptin and dynorphin, which are excitatory and inhibitory to GnRH secretion, respectively, remained unaltered in KPRKO mice compared to WT controls. Together, these findings show that the near-complete loss of PGR signaling from KNDy cells does not affect negative feedback regulation of GnRH pulse generation in mice, suggesting that feedback through this receptor can occur via a small number of KNDy cells or a yet unidentified cell population.

[Is there still a place for progesterone receptor modulators in chronic use ?] / Cas clinique. Y a-t-il encore une place pour les modulateurs du récepteur de la progestérone en continu ?

Selective progesterone receptor modulators (SPRMs) are synthetic steroid compounds that interact with the progesterone receptor, inducing various agonist, antagonist or mixed responses. First identified with mifepristone, they are now represented by ulipristal acetate (UPA), used for emergency contraception and uterine fibroids. Despite a few rare cases of severe hepatic insufficiency, SPRMs offer advantages in the treatment of uterine fibroids, reducing their volume without the hypoestrogenic side-effects of GnRH agonists, thus preserving patients' bone capital and quality of life. Despite temporary suspension of UPA administrated on a daily basis, research is exploring the potential of SPRMs in the management of endometriosis, adenomyosis and breast cancer. Despite certain concerns, SPRMs offer promising prospects in gynecological pathologies, opening up new therapeutic avenues to improve women's health and quality of life. This article describes the case of a patient with peritoneal leiomyomatosis for whom UPA significantly alleviated symptoms, reduced disease progression and improved quality of life, even allowing a pregnancy.

Les modulateurs sélectifs des récepteurs de la progestérone (SPRMs) sont des composés stéroïdiens synthétiques qui interagissent via le récepteur de la progestérone, induisant diverses réponses, agonistes, antagonistes ou mixtes. Les SPRMs ont d'abord été représentés par la mifépristone, utilisée pour ses propriétés antagonistes dans la gestion de l'interruption de la grossesse, puis par l'acétate d'ulipristal, qui est indiqué en contraception d'urgence, mais aussi pour la gestion de myomes utérins symptomatiques. Les SPRMs permettent de réduire le volume des myomes utérins, sans induire les effets secondaires d'hypo-œstrogénie des agonistes de la GnRH, préservant ainsi le capital osseux et la qualité de vie des patientes. Néanmoins, quelques cas graves d'insuffisance hépatique ont conduit à la suspension temporaire de l'acétate d'ulipristal en traitement chronique. En dépit de certaines réserves, les SPRMs offrent des perspectives dans les affections gynécologiques, ouvrant de nouvelles voies thérapeutiques pour améliorer la santé et la qualité de vie des femmes. Des recherches explorent leur potentiel dans l'endométriose, l'adénomyose et la chimioprévention du cancer du sein. Nous décrivons ici le cas d'une patiente avec léiomyomatose péritonéale pour laquelle l'acétate d'ulipristal a significativement réduit les symptômes et l'évolution de la maladie, tout en améliorant la qualité de vie de la patiente, avec même l'obtention d'une grossesse menée à terme.

Radiotherapy is recommended for hormone receptor-negative older breast cancer patients after breast conserving surgery.

In this study, the necessity of radiotherapy (RT) for hormone receptor-negative older breast cancer patients after breast-conserving surgery (BCS) was investigated. The data of hormone receptor-negative invasive breast cancer patients who underwent BCS were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All patients were separated into two groups, namely, the RT group and the no radiotherapy (No RT) group. The 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were compared between the No RT and RT groups after propensity score matching (PSM). The nomograms for predicting the survival of patients were constructed from variables identified by univariate or multivariate Cox regression analysis. A total of 2504 patients were enrolled in the training cohort, and 630 patients were included in the validation cohort. After PSM, 738 patients were enrolled in the No RT group and RT group. We noted that RT can improve survival in hormone receptor-negative older breast cancer patients who undergo BCS. Based on the results of multivariate Cox analysis, age, race, tumour grade, receipt of RT and chemotherapy, pathological T stage, N status, M status and HER2 status were linked to OS and CSS for these patients, and nomograms for predicting OS and CSS were constructed and validated. Moreover, RT improved OS and CSS in hormone receptor-negative older breast cancer patients who underwent BCS. In addition, the proposed nomograms more accurately predicted OS and CSS for hormone receptor-negative older breast cancer patients after BCS.

PIK3CA mutational status in tissue and plasma as a prognostic biomarker in HR+/HER2- breast cancer.

INTRODUCTION: Hotspots (HS) mutations in the PIK3CA gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early-stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma approaches and to analyze the prognostic impact of PIK3CA mutations (PIK3CAm) in HR+/HER2- BC. METHODS: A retrospective and unicentric analysis of PIK3CA mutational status in tissue and plasma samples by Cobas®PIK3CA Mutation Kit in patients with HR+/HER2- BC. RESULTS: We analyzed 225 samples from 161 patients with luminal BC. PIK3CA mutations were identified in 62 patients (38.5%), of which 39.6% were found in tissue and 11.8% in plasma. In advanced disease, plasma and tissue correlation rate was performed in 64 cases, with an overall agreement of 70.3%. Eighty patients were treated with CDK4/6 inhibitors + endocrine therapy. We observed a moderately worse progression-free survival (PFS) in PIK3CAm versus wild-type (WT) (24 m vs. 30 m; HR = 1.39, p = 0.26). A subanalysis was carried out based on exons 9 and 20, which showed a statistically poorer PFS in PIK3CAm exon 9 versus 20 population (9.7 m vs. 30.3 m; HR = 2.84; p = 0.024). Furthermore, detection of PIK3CAm in plasma was linked to a worse PFS vs PIK3CAm detection just in tissue (12.4 vs. 29.3; HR = 2.4; p = 0.08). CONCLUSIONS: Our findings suggest the PIK3CA evaluation in tissue as the diagnostic method of choice, however, additional investigations are required to improve the role of liquid biopsy in the PIK3CA assessment. PIK3CAm show worse outcomes in advanced luminal BC, especially in exon 9 mutation carriers, despite visceral involvement, prior exposure to endocrine therapy or detection of PIK3CAm in plasma, with an unclear prognosis in early-stage disease. Nonetheless, this should be validated in a prospective cohort study.

Clinicopathological characteristics, treatment patterns and outcomes in patients with HER2-positive breast cancer based on hormone receptor status: a retrospective study.

BACKGROUND: Different hormone receptor (HR) expression patterns have significant biological and therapeutic implications in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, the distinction between HR-positive /HER2-positive (HR+/HER2+) and HR-negative/HER2-positive (HR-/HER2+) subtypes remains unclear. METHODS: This retrospective study analyzed 828 patients with HER2-positive breast cancer at the First Affiliated Hospital of Xi'an Jiaotong University from 2012 to 2022. Baseline characteristics were compared by chi-square test. Survival outcomes were estimated by Kaplan-Meier method. RESULTS: In total, 56.3% (n = 466) had HR-positive and 43.7% (n = 362) had HR-negative disease. Comparatively, HR+/HER2 + breast cancers presented favorable clinicopathological features. At a median follow-up of 49 months, 199 disease-free survival (DFS) events and 99 deaths were observed. HR+/HER2 + patients had significantly better survival outcomes than HR-/HER2 + patients. HR-positive status was an independent protective factor for overall survival (OS) [P = 0.032; hazard ratio, 0.61; 95% confidence interval (CI), 0.39-0.96] and DFS (P = 0.001; hazard ratio, 0.61; 95% CI, 0.46-0.81). HR+/HER2 + patients were significantly less sensitive to neoadjuvant therapy than HR-/HER2 + patients. In the first-line treatment for HR+/HER2 + advanced breast cancer, receiving endocrine therapy significantly improved advanced-OS (P < 0.001; hazard ratio, 0.33; 95% CI, 0.18-0.59) and progression-free survival (PFS) (P < 0.001; hazard ratio, 0.38; 95% CI, 0.25-0.58) compared with not receiving endocrine therapy. Moreover, maintenance endocrine therapy after HER2-targeted therapy and chemotherapy is associated with significant advanced-OS and PFS benefits compared with no maintenance endocrine therapy (advanced-OS: P < 0.001; hazard ratio, 0.05; 95% CI, 0.03-0.12; PFS: P < 0.001; hazard ratio, 0.35; 95% CI, 0.21-0.57). CONCLUSIONS: This study reveals the high heterogeneity of HER2-positive breast cancer related to HR status in clinicopathological features, metastasis patterns, and outcomes. Large randomized controlled trials are warranted to optimize treatment strategies for the HER2-positive breast cancer population.

On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Patients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies. METHODS: On-treatment biopsies from 297 patients with invasive BC in three randomized, prospective neoadjuvant trials were assessed (GeparQuattro, GeparQuinto, GeparSixto). BC quantity, tumor-infiltrating lymphocytes (TILs), and the proliferation marker Ki-67 were compared to pre-treatment samples. The study investigated the correlation between residual cancer, changes in Ki-67 and TILs, and their impact on pathologic complete response (pCR) and disease-free survival (DFS). RESULTS: Among the 297 samples, 138 (46%) were hormone receptor-positive (HR+)/human epidermal growth factor 2-negative (HER2-), 87 (29%) were triple-negative (TNBC), and 72 (24%) were HER2+. Invasive tumor cells were found in 70% of on-treatment biopsies, with varying rates across subtypes (HR+/HER2-: 84%, TNBC: 62%, HER2+: 51%; p < 0.001). Patients with residual tumor on-treatment had an 8% pCR rate post-treatment (HR+/HER2-: 3%, TNBC: 19%, HER2+: 11%), while those without any invasive tumor had a 50% pCR rate (HR+/HER2-: 27%; TNBC: 48%, HER2+: 66%). Sensitivity for predicting residual disease was 0.81, with positive and negative predictive values of 0.92 and 0.50, respectively. Increasing TILs from baseline to on-treatment biopsy (if residual tumor was present) were linked to higher pCR likelihood in the overall cohort (OR 1.034, 95% CI 1.013-1.056 per % increase; p = 0.001) and with a longer DFS in TNBC (HR 0.980, 95% CI 0.963-0.997 per % increase; p = 0.026). Persisting or increased Ki-67 was associated with with lower pCR probability in the overall cohort (OR 0.957, 95% CI 0.928-0.986; p = 0.004) and shorter DFS in TNBC (HR 1.023, 95% CI 1.001-1.047; p = 0.04). CONCLUSION: On-treatment biopsies can predict patients unlikely to achieve pCR post-therapy. This could facilitate therapy adjustments for TNBC or HER2 + BC. They also might offer insights into therapy resistance mechanisms. Future research should explore whether standardized or expanded sampling enhances the accuracy of on-treatment biopsy procedures. Trial registration GeparQuattro (EudraCT 2005-001546-17), GeparQuinto (EudraCT 2006-005834-19) and GeparSixto (EudraCT 2011-000553-23).

Real-world treatment patterns and outcomes in patients with HR+/HER2- metastatic breast cancer treated with chemotherapy in the United States.

BACKGROUND: Until recently, treatment options for patients with hormone receptor-positive/human epidermal growth factor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) and resistance to endocrine therapy were limited to chemotherapy. This real-world study describes treatment patterns and outcomes in patients treated with chemotherapy in the United States before approval of antibody-drug conjugates. PATIENTS AND METHODS: This retrospective, observational study included adults with HR+/HER2- mBC from the ConcertAI Patient360™ Breast Cancer dataset who initiated their first chemotherapy in the metastatic setting between January 2011 and June 2021. Treatment patterns were described; real-world overall survival, time to next treatment or death, and real-world progression-free survival were evaluated for all eligible patients and patients treated with subsequent chemotherapy. Index dates were the start date of each chemotherapy treatment. RESULTS: Among 1545 eligible patients, 76% were white, 12% had Eastern Cooperative Oncology Group performance status ≥2, 38% had de novo mBC, and median age was 61 years (range, 52-69 years). Within the index period, capecitabine was used the most as the first chemotherapy agent and decreased in later treatments, while the use of eribulin increased between first and fourth chemotherapies. Median (95% confidence interval) real-world overall survival was 23.3 months (21.3-25.4 months) from start of first chemotherapy, time to next treatment or death was 6.5 months (5.9-7.1 months), and real-world progression-free survival was 6.9 months (6.4-7.6 months); median times from second, third, and fourth chemotherapies decreased with each additional chemotherapy treatment. CONCLUSIONS: This real-world study demonstrates that for patients with HR+/HER2- mBC, chemotherapy provides relatively limited survival benefit which decreases with each additional chemotherapy line, and highlights the need for improved treatment options.