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1.
Aging Male ; 27(1): 2391380, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-39140708

RÉSUMÉ

BACKGROUND: Direct evidence for the relationship between a large prostate (≥80 ml) and androgen receptor/PSA signal remains lacking in benign prostatic hyperplasia (BPH). Our aim is to identify whether the cause of a large prostate is related to progesterone receptor (PGR) androgen receptor (AR), oestrogen receptor α, ß (ERα,ß) and prostate-specific antigen (PSA). MATERIALS AND METHODS: Surgical specimens of BPH in plasmakinetic resection of the prostate (PKRP) with three groups of different prostate-sizes with mean volumes of 25.97 ml, 63.80 ml, and 122.37 ml were collected for immunohistochemical analysis of the tissue microarray with PGR, AR, PSA and ERs. Rats were castrated and treated with testosterone replacement to explore androgen and PGR, AR and ERs expression levels in the prostate. Quantitative real-time reverse transcription polymerase chain reaction (Rt-PCR) for mRNA detection of above genes was conducted. RESULTS: Immunoblotting, Rt-PCR and immunohistochemistry assays showed that PGR, PSA, AR, ERα expression levels were positively correlated with prostate size and that ERß expression levels were negatively correlated with prostate volume. Animal experiments have shown that prostate volume is decreased in castrated rats with decreased PGR, AR, ERα and increased ERß expression levels. CONCLUSION: PGR, AR, ERs signals can be regarded as important factors for large-sized prostates in BPH patients (≥100 ml).


Sujet(s)
Modèles animaux de maladie humaine , Récepteur alpha des oestrogènes , Antigène spécifique de la prostate , Prostate , Hyperplasie de la prostate , Récepteurs aux androgènes , Récepteurs à la progestérone , Mâle , Hyperplasie de la prostate/métabolisme , Hyperplasie de la prostate/anatomopathologie , Animaux , Récepteurs aux androgènes/métabolisme , Récepteurs à la progestérone/métabolisme , Récepteurs à la progestérone/analyse , Rats , Humains , Antigène spécifique de la prostate/sang , Sujet âgé , Récepteur alpha des oestrogènes/métabolisme , Récepteur alpha des oestrogènes/analyse , Prostate/métabolisme , Prostate/anatomopathologie , Rat Sprague-Dawley , Adulte d'âge moyen , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Récepteur bêta des oestrogènes/métabolisme , Récepteur bêta des oestrogènes/analyse , Taille d'organe
2.
Breast ; 77: 103769, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39043079

RÉSUMÉ

BACKGROUND: Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET). PATIENTS AND METHODS: The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, aiming to evaluate ET choices for premenopausal patients affected by hormone receptor-positive eBC in a real-world setting. Here we report also the results in terms of type of ET prescribed according to the definition of high-risk patients by monarchE and NATALEE trials. RESULTS: Between October 2019 and June 2022, 600 premenopausal patients were included, with a median age of 46 years. Almost half (271, 45.2 %) of the patients had stage I disease, while 254 (42.3 %) and 60 (10.0 %) patients had stage II and III, respectively. Overall, 149 (25.1 %) patients received tamoxifen alone, 83 (14.0 %) tamoxifen with ovarian function suppression (OFS), while 361 (60.9 %) received aromatase inhibitor (AI) with OFS. Patients treated with AI and OFS had higher number of metastatic axillary nodes, higher grade and more often received chemotherapy (all p < 0.001). According to the inclusion criteria of the monarchE and NATALEE trials, 81 patients (15.6 %) were considered high-risk for the monarchE and received AI with OFS in 88.9 % of the cases, while 231 patients (44.4 %) were considered high-risk for the NATALEE trial and received AI with OFS in 74.5 % of cases. CONCLUSIONS: AI with OFS is the most prescribed adjuvant ET among premenopausal patients, especially in the presence of high-risk features.


Sujet(s)
Antinéoplasiques hormonaux , Inhibiteurs de l'aromatase , Tumeurs du sein , Préménopause , Tamoxifène , Humains , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Adulte d'âge moyen , Études prospectives , Traitement médicamenteux adjuvant , Tamoxifène/usage thérapeutique , Antinéoplasiques hormonaux/usage thérapeutique , Inhibiteurs de l'aromatase/usage thérapeutique , Adulte , Italie , Stadification tumorale , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse
4.
J Mater Chem B ; 12(29): 7135-7142, 2024 Jul 24.
Article de Anglais | MEDLINE | ID: mdl-38952205

RÉSUMÉ

Fluorescence-image guided surgery (FGS) can intraoperatively provide real-time visualization of a tumor incisal edge and high-resolution identification of tumor foci to improve treatment outcomes. In this contribution, we report a fluorescent probe NB-TAM based on intramolecularly folded photoinduced electron transfer (PET), which displayed a prominent turn-on response in the near-infrared (NIR) window upon specific interaction with the estrogen receptor (ER). Significantly, NB-TAM could delineate a clear tumor incisal edge (tumor-to-normal tissue ratio > 5) in a 70-min time window, and was successfully used to guide the facile and precise resection of ER+ breast tumors in mice. To our surprise, NB-TAM was found to be capable of identifying very tiny lung metastatic ER+ breast tumor foci (0.4 × 0.3 mm), and this ultrahigh resolution was essential to effectively promote tumor resection precision and early diagnosis of tiny tumors. These results clearly elucidate the promising application of NB-TAM as a diagnostic agent for intraoperative fluorescence imaging of ER+ breast cancer.


Sujet(s)
Tumeurs du sein , Colorants fluorescents , Imagerie optique , Récepteurs des oestrogènes , Animaux , Colorants fluorescents/composition chimique , Femelle , Tumeurs du sein/anatomopathologie , Tumeurs du sein/imagerie diagnostique , Humains , Souris , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Souris de lignée BALB C , Souris nude
5.
Acta Oncol ; 63: 535-541, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38967128

RÉSUMÉ

BACKGROUND: Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients. PATIENTS AND METHODS: Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done. RESULTS: After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM.  Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.


Sujet(s)
Antinéoplasiques hormonaux , Tumeurs du sein , Récepteurs des oestrogènes , Récepteurs à la progestérone , Tamoxifène , Humains , Tamoxifène/usage thérapeutique , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/mortalité , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Femelle , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Études de suivi , Adulte d'âge moyen , Antinéoplasiques hormonaux/usage thérapeutique , Récepteurs à la progestérone/métabolisme , Traitement médicamenteux adjuvant/méthodes , Sujet âgé , Post-ménopause , Adulte , Résultat thérapeutique
6.
JAMA Netw Open ; 7(7): e2423435, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-39058489

RÉSUMÉ

Importance: There are insufficient data comparing 16α-18F-fluoro-17ß-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence. Objective: To determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence. Design, Setting, and Participants: This diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024. Exposure: Participants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm. Main Outcomes and Measures: The outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences. Results: A total of 124 patients were accrued, with 62 in cohort 1 (median [IQR] age, 52 [32-84] years) and 62 in cohort 2 (median [IQR] age, 66 [30-93] years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 (P > .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 (P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 (P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT (P = .13). Conclusions and Relevance: In this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.


Sujet(s)
Tumeurs du sein , Récidive tumorale locale , Stadification tumorale , Tomographie par émission de positons couplée à la tomodensitométrie , Humains , Femelle , Tumeurs du sein/imagerie diagnostique , Tumeurs du sein/anatomopathologie , Adulte d'âge moyen , Récidive tumorale locale/imagerie diagnostique , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Sujet âgé , Adulte , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Oestradiol/analogues et dérivés
7.
Gan To Kagaku Ryoho ; 51(6): 651-653, 2024 Jun.
Article de Japonais | MEDLINE | ID: mdl-39009524

RÉSUMÉ

The patient, an 83-year-old woman, was diagnosed with ER- and PgR-positive left breast cancer(T2N0M0, Stage ⅡA) at the age of 68. At the time, she underwent preoperative chemotherapy followed by Bp+Ax and postoperative radiotherapy to the conserved breast. She also received endocrine therapy as adjuvant therapy. At the age of 73, she underwent radiotherapy for multiple bone metastases and left axillary lymphadenectomy due to left axillary lymph node recurrence. After surgery, she received 4 regimens of endocrine therapy over a period of 5 years and 1 month for bone metastases. At the age of 79, S-1 was administered for pulmonary metastasis which continued for the next 2 years and 8 months. At the age of 81, palbociclib+letrozole were administered for 1 year and 8 months owing to the progression of bone metastases. At the age of 83, she developed liver metastases and was administered ethinyl estradiol, starting at 1.5 mg/day and continued at a reduced dose of 0.5 mg/day for 9 months. The reduction in tumor markers after treatment initiation was rapid, and there were no serious adverse events. Ethinyl estradiol was useful for maintaining QOL in this elderly patient with recurrent breast cancer.


Sujet(s)
Tumeurs du sein , Éthinyloestradiol , Récidive , Humains , Femelle , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Éthinyloestradiol/administration et posologie , Éthinyloestradiol/usage thérapeutique , Sujet âgé de 80 ans ou plus , Récepteurs des oestrogènes/analyse , Antinéoplasiques hormonaux/usage thérapeutique , Antinéoplasiques hormonaux/administration et posologie , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Récepteurs à la progestérone/métabolisme
8.
Breast ; 77: 103777, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-39038425

RÉSUMÉ

BACKGROUND: Early invasive ductal carcinoma (IDC) breast cancer often presents with a coexisting ductal carcinoma in situ (DCIS) component, while about 5 % of cases present with an extensive (>25 %) intraductal component (EIC). The impact of EIC on the genomic risk of recurrence is unclear. METHODS: Patients with early hormone receptor-positive HER2neu-negative (HR + HER2-) IDC breast cancer and a known OncotypeDX Breast Recurrence Score® (RS) who underwent breast surgery at our institute were included. Using a rule-based text-analysis algorithm, we analyzed pathological reports and categorized patients into three groups: EIC, non-extensive DCIS (DCIS-L), and pure-IDC (NO-DCIS). Genomic risk was determined using OncotypeDX RS. RESULTS: A total of 33 (4.6 %) EIC cases, 377 (57.2 %) DCIS-L cases and 307 (42.8 %) NO-DCIS cases were identified. Patients in the EIC group were younger and had lower tumor grades than other groups. The distribution of genomic risk varied between the groups, with EIC tumors significantly less likely to have a high RS (>25) compared to DCIS-L and No-DCIS tumors (3 % vs 20 % and 20 %, respectively; p = 0.03). When adjusted to age, tumor size, grade and LNs involvement, both DCIS-L and NO-DCIS groups were significantly correlated with a higher probability of high RS compared to the EIC group (OR 12.3 and OR 13.1, respectively; p < 0.02). Moreover, patients with EIC had a lower likelihood for adjuvant chemotherapy recommendation. CONCLUSIONS: In early HR + HER2- IDC, an EIC correlates with a reduced genomic recurrence risk. The impact on genomic risk seems to be influenced by the extent, not merely the presence, of DCIS.


Sujet(s)
Tumeurs du sein , Carcinome canalaire du sein , Carcinome intracanalaire non infiltrant , Récidive tumorale locale , Humains , Femelle , Tumeurs du sein/génétique , Tumeurs du sein/anatomopathologie , Tumeurs du sein/chirurgie , Adulte d'âge moyen , Récidive tumorale locale/génétique , Carcinome intracanalaire non infiltrant/génétique , Carcinome intracanalaire non infiltrant/anatomopathologie , Carcinome canalaire du sein/génétique , Carcinome canalaire du sein/anatomopathologie , Carcinome canalaire du sein/chirurgie , Sujet âgé , Adulte , Récepteur ErbB-2/génétique , Récepteur ErbB-2/métabolisme , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Récepteurs à la progestérone/métabolisme , Appréciation des risques , Études rétrospectives , Génomique , Facteurs de risque
9.
J Clin Oncol ; 42(25): 3012-3021, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-38833643

RÉSUMÉ

PURPOSE: Phosphatidylinositol 3-kinase/AKT-serine threonine kinase/mammalian target of rapamycin (mTOR) pathway abnormalities contribute to endocrine resistance. Everolimus, an mTOR inhibitor, improved progression-free survival in hormone receptor-positive metastatic breast cancer (BC) when combined with endocrine therapy (ET). In this phase III randomized, placebo-controlled trial, we assessed the efficacy of everolimus + ET as adjuvant therapy in high-risk, hormone receptor-positive, human epidermal growth factor receptor 2-negative BC after adjuvant/neoadjuvant chemotherapy. METHODS: Patients were randomly assigned 1:1 to physician's choice ET and 1 year of everolimus (10 mg orally once daily) or placebo stratified by risk group. The primary end point was invasive disease-free survival (IDFS) evaluated by a stratified log-rank test with the hazard ratio (HR) estimated by Cox regression. Subset analyses included preplanned evaluation by risk group and exploratory analyses by menopausal status and age. Secondary end points included overall survival (OS) and safety. Everolimus did not improve IDFS/OS when added to ET in patients with early-stage high-risk, hormone receptor-positive BC. RESULTS: One thousand and nine hundred thirty-nine patients were randomly assigned with 1,792 eligible for analysis. Overall, no benefit of everolimus was seen for IDFS (HR, 0.94 [95% CI, 0.77 to 1.14]) or OS (HR, 0.97 [95% CI, 0.75 to 1.26]). The assumption of proportional hazards was not met suggesting significant variability in the HR over time since the start of treatment. In an unplanned subgroup analysis among postmenopausal patients (N = 1,221), no difference in IDFS (HR, 1.08 [95% CI, 0.86 to 1.36]) or OS (HR, 1.19 [95% CI, 0.89 to 1.60]) was seen. In premenopausal patients (N = 571), everolimus improved both IDFS (HR, 0.64 [95% CI, 0.44 to 0.94]) and OS (HR, 0.49 [95% CI, 0.28 to 0.86]). Treatment completion rates were lower in the everolimus arm compared with placebo (48% v 73%) with higher grade 3 and 4 adverse events (35% v 7%). CONCLUSION: One year of adjuvant everolimus + ET did not improve overall outcomes. Subset analysis suggests mTOR inhibition as a possible target for patients who remain premenopausal after chemotherapy.


Sujet(s)
Tumeurs du sein , Évérolimus , Humains , Évérolimus/usage thérapeutique , Évérolimus/effets indésirables , Évérolimus/administration et posologie , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/mortalité , Femelle , Adulte d'âge moyen , Sujet âgé , Adulte , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Récepteur ErbB-2/métabolisme , Récepteurs à la progestérone/métabolisme , Stadification tumorale , Traitement médicamenteux adjuvant , Antinéoplasiques hormonaux/usage thérapeutique , Antinéoplasiques hormonaux/effets indésirables
10.
Medicina (Kaunas) ; 60(6)2024 Jun 07.
Article de Anglais | MEDLINE | ID: mdl-38929568

RÉSUMÉ

Background and Objectives: Patients with human epidermal growth factor receptor 2 (HER2) -positive, hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) usually undergo trastuzumab emtansine (T-DM1) therapy in subsequent lines. Combining endocrine therapy (ET) with T-DM1 can improve treatment outcomes in this subtype. Therefore, this study aimed to investigate the benefits of using T-DM1 with ET in HER2-positive and HR-positive MBC. This study was the first to investigate the benefits of combining ET with T-DM1. Material and Methods: This study analyzed the medical records of patients with HER2-positive and HR-positive MBC who were treated with T-DM1 from June 2010 to December 2021. The patients were divided into groups based on whether they received concomitant ET with T-DM1. The primary endpoint was to determine the progression-free survival (PFS), while the secondary endpoints were overall survival (OS), objective response rate, and safety of the treatment. Results: Our analysis examined 88 patients, of whom 32 (36.4%) were treated with T-DM1 in combination with ET. The combination therapy showed a significant improvement in median PFS (15.4 vs. 6.4 months; p = 0.00004) and median OS (35.0 vs. 23.1 months; p = 0.026) compared to T-DM1 alone. The ORR was also higher in the combination group (65.6% vs. 29.3%; p = 0.026). Patients treated with pertuzumab priorly had reduced median PFS on T-DM1 compared to those who were not treated with pertuzumab (11.7 vs. 5.4 months, respectively; p < 0.01). T-DM1 demonstrated better median PFS in HER2 3+ patients compared to HER2 2+ patients, with an amplification ratio of >2.0 (10.8 vs 5.8 months, respectively; p = 0.049). The safety profiles were consistent with previous T-DM1 studies. Conclusions: The combination of T-DM1 with ET can significantly improve PFS and OS in patients with HER2-positive and HR-positive MBC. Our study suggests that prior pertuzumab treatment plus trastuzumab treatment might decrease T-DM1 efficacy.


Sujet(s)
Ado-trastuzumab emtansine , Tumeurs du sein , Survie sans progression , Récepteur ErbB-2 , Humains , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/mortalité , Femelle , Adulte d'âge moyen , Récepteur ErbB-2/analyse , Ado-trastuzumab emtansine/usage thérapeutique , Sujet âgé , Adulte , Études rétrospectives , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/pharmacologie , Antinéoplasiques immunologiques/usage thérapeutique , Antinéoplasiques immunologiques/pharmacologie , Métastase tumorale , Sujet âgé de 80 ans ou plus , Trastuzumab/usage thérapeutique , Récepteurs des oestrogènes/analyse , Récepteurs des oestrogènes/métabolisme
11.
J Clin Oncol ; 42(24): 2887-2898, 2024 Aug 20.
Article de Anglais | MEDLINE | ID: mdl-38824432

RÉSUMÉ

PURPOSE: ASCO/College of American Pathologists guidelines recommend reporting estrogen receptor (ER) and progesterone receptor (PgR) as positive with (1%-100%) staining. Statistically standardized quantitated positivity could indicate differential associations of positivity with breast cancer outcomes. METHODS: MA.27 (ClinicalTrials.gov identifier: NCT00066573) was a phase III adjuvant trial of exemestane versus anastrozole in postmenopausal women with early-stage breast cancer. Immunochemistry ER and PgR HSCORE and % positivity (%+) were centrally assessed by machine image quantitation and statistically standardized to mean 0 and standard deviation (SD) 1 after Box-Cox variance stabilization transformations of square for ER; for PgR, (1) natural logarithm (0.1 added to 0 HSCOREs and 0%+) and (2) square root. Our primary end point was MA.27 distant disease-free survival (DDFS) at a median 4.1-year follow-up, and secondary end point was event-free survival (EFS). Univariate survival with cut points at SDs about a mean of 0 (≤-1; (-1, 0]; (0, 1]; >1) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions had two-sided Wald tests and nominal significance P < .05. RESULTS: Of 7,576 women accrued, 3,048 women's tumors had machine-quantitated image analysis results: 2,900 (95%) for ER, 2,726 (89%) for PgR, and 2,582 (85% of 3,048) with both ER and PgR. Higher statistically standardized ER and PgR HSCORE and %+ were associated with better univariate DDFS and EFS (P < .001). In multivariable assessments, ER HSCORE and %+ were not significantly associated (P = .52-.88) with DDFS in models with PgR, whereas higher PgR HSCORE and %+ were significantly associated with better DDFS (P = .001) in models with ER. CONCLUSION: Adjunctive statistical standardization differentiated quantitated levels of ER and PgR. Patients with higher ER- and PgR-standardized units had superior DDFS compared with those with HSCOREs and %+ ≤-1.


Sujet(s)
Anastrozole , Androstadiènes , Tumeurs du sein , Post-ménopause , Récepteurs des oestrogènes , Récepteurs à la progestérone , Humains , Femelle , Anastrozole/usage thérapeutique , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/mortalité , Récepteurs à la progestérone/métabolisme , Récepteurs à la progestérone/analyse , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Androstadiènes/usage thérapeutique , Androstadiènes/administration et posologie , Adulte d'âge moyen , Sujet âgé , Canada , Traitement médicamenteux adjuvant , Survie sans rechute
12.
Breast ; 76: 103761, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38880077

RÉSUMÉ

BACKGROUND: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. METHODS: First-line endocrine-sensitive, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) patients received palbociclib capsules plus fulvestrant or letrozole. The primary endpoint was progression-free survival (PFS). This post-hoc analysis compared PPI use. Patients were PPI-naïve (N-PPI) if not on PPI during the study, and either early (E-PPI) or long-term PPI (LT-PPI) if on PPI at study entry or for at least ≥⅔ of treatment, respectively. PPI groups were not mutually exclusive. RESULTS: Among 486 patients, 66.9 % were N-PPI, 13.2 % E-PPI, 18.7 % LT-PPI, and 11.5 % of the PPI users were defined as neither. Median PFS (mPFS) was 29.6 months in the study population, 28.7 months in N-PPI, 23.0 months in E-PPI (Hazard Ratio [HR] 1.5; 95%Confidence Interval [CI] 1.1-2.2; p = 0.024), and 23.0 months in LT-PPI (HR 1.4; 95%CI 1.0-1.9; p = 0.035). By landmark analysis, PPI use was associated with poorer mPFS at 3 and 12 months. Grade ≥3 hematological adverse events occurred in 71.7 % of N-PPI, 57.8 % of E-PPI (p = 0.021), and 54.9 % of LT-PPI (p = 0.003). Dose reductions and dosing delays due to hematological toxicity occurred in 70.8 % of N-PPI, 56.3 % of E-PPI (p = 0.018), and 52.7 % of LT-PPI (p = 0.002). CONCLUSIONS: PPI use may reduce palbociclib capsule toxicity, dose modifications, and clinical activity in HR+/HER2- ABC.


Sujet(s)
Protocoles de polychimiothérapie antinéoplasique , Tumeurs du sein , Fulvestrant , Létrozole , Pipérazines , Inhibiteurs de la pompe à protons , Pyridines , Récepteur ErbB-2 , Récepteurs des oestrogènes , Humains , Pyridines/administration et posologie , Pyridines/usage thérapeutique , Femelle , Pipérazines/administration et posologie , Pipérazines/usage thérapeutique , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Adulte d'âge moyen , Sujet âgé , Récepteur ErbB-2/métabolisme , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Létrozole/administration et posologie , Inhibiteurs de la pompe à protons/administration et posologie , Adulte , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Fulvestrant/administration et posologie , Fulvestrant/usage thérapeutique , Survie sans progression , Récepteurs à la progestérone/métabolisme , Sujet âgé de 80 ans ou plus
13.
J Clin Oncol ; 42(22): 2680-2690, 2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-38889373

RÉSUMÉ

PURPOSE: AMEERA-5 investigated amcenestrant (oral selective estrogen receptor [ER] degrader) plus palbociclib versus letrozole plus palbociclib as first-line treatment for ER-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced/metastatic breast cancer (aBC). MATERIALS AND METHODS: In AMEERA-5 (ClinicalTrials.gov identifier: NCT04478266), a double-blind, double-dummy, international phase III trial, adult pre-/post-menopausal women and men without previous systemic therapy for ER+/HER2- aBC were randomly assigned 1:1 to amcenestrant 200 mg once daily + standard palbociclib dosage (125 mg once daily, 21 days on/7 days off) or letrozole 2.5 mg once daily + standard palbociclib dosage, stratified by de novo metastatic disease, postmenopausal women, and visceral metastasis. The primary end point was progression-free survival (PFS), compared using a stratified log-rank test with one-sided type I error rate of 2.5%. Secondary end points included overall survival (key secondary), pharmacokinetics, and safety. RESULTS: Between October 14, 2020, and December 2, 2021, 1,068 patients were randomly assigned to amcenestrant + palbociclib (N = 534) or letrozole + palbociclib (N = 534). At the interim analysis (median follow-up 8.4 months), the stratified hazard ratio for PFS was 1.209 (95% CI, 0.939 to 1.557; one-sided P value = .9304); therefore, the study was stopped for futility. The 6-month PFS rate was 82.7% (95% CI, 79.0 to 85.8) with amcenestrant + palbociclib versus 86.9% (95% CI, 83.5 to 89.6) with letrozole + palbociclib. In the amcenestrant + palbociclib versus letrozole + palbociclib groups, treatment-emergent adverse events (any grade) occurred in 85.6% versus 85.4% of patients and grade ≥3 events in 46.3% versus 60.8%, respectively. CONCLUSION: The AMEERA-5 study was discontinued on the basis of the recommendation of the data monitoring committee at the interim futility analysis. No new safety signals were identified.


Sujet(s)
Protocoles de polychimiothérapie antinéoplasique , Tumeurs du sein , Létrozole , Pipérazines , Pyridines , Récepteur ErbB-2 , Récepteurs des oestrogènes , Humains , Femelle , Létrozole/administration et posologie , Létrozole/usage thérapeutique , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Adulte d'âge moyen , Pyridines/usage thérapeutique , Pyridines/administration et posologie , Pyridines/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Récepteur ErbB-2/métabolisme , Récepteur ErbB-2/analyse , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Sujet âgé , Pipérazines/usage thérapeutique , Pipérazines/administration et posologie , Pipérazines/effets indésirables , Méthode en double aveugle , Adulte , Mâle , Tumeur du sein de l'homme/traitement médicamenteux , Tumeur du sein de l'homme/anatomopathologie , Tumeur du sein de l'homme/métabolisme , Sujet âgé de 80 ans ou plus
14.
Radiother Oncol ; 197: 110379, 2024 08.
Article de Anglais | MEDLINE | ID: mdl-38862080

RÉSUMÉ

BACKGROUND: Breast cancer is a leading cause of cancer-related deaths in females, and the hormone receptor-positive subtype is the most frequent. Breast cancer is a common source of brain metastases; therefore, we aimed to generate a brain metastases prediction model in females with hormone receptor-positive breast cancer. METHODS: The primary cohort included 3,682 females with hormone receptor-positive breast cancer treated at a single center from May 2009 to May 2020. Patients were randomly divided into a training dataset (n = 2,455) and a validation dataset (n = 1,227). In the training dataset, simple logistic regression analyses were used to measure associations between variables and the diagnosis of brain metastases and to build multivariable models. The model with better calibration and discrimination capacity was tested in the validation dataset to measure its predictive performance. RESULTS: The variables incorporated in the model included age, tumor size, axillary lymph node status, clinical stage at diagnosis, HER2 expression, Ki-67 proliferation index, and the modified Scarff-Bloom-Richardson grade. The area under the curve was 0.81 (95 % CI 0.75-0.86), p < 0.001 in the validation dataset. The study presents a guide for the clinical use of the model. CONCLUSION: A brain metastases prediction model in females with hormone receptor-positive breast cancer helps assess the individual risk of brain metastases.


Sujet(s)
Tumeurs du cerveau , Tumeurs du sein , Humains , Femelle , Tumeurs du sein/anatomopathologie , Tumeurs du cerveau/secondaire , Adulte d'âge moyen , Appréciation des risques , Sujet âgé , Récepteur ErbB-2/métabolisme , Adulte , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Récepteurs à la progestérone/métabolisme
15.
J Clin Oncol ; 42(23): 2812-2821, 2024 Aug 10.
Article de Anglais | MEDLINE | ID: mdl-38771995

RÉSUMÉ

PURPOSE: A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). METHODS: In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS). RESULTS: Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm. CONCLUSION: First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.


Sujet(s)
Aminopyridines , Protocoles de polychimiothérapie antinéoplasique , Tumeurs du sein , Purines , Récepteur ErbB-2 , Récepteurs des oestrogènes , Récepteurs à la progestérone , Humains , Femelle , Aminopyridines/administration et posologie , Aminopyridines/effets indésirables , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Récepteur ErbB-2/métabolisme , Récepteur ErbB-2/analyse , Adulte d'âge moyen , Adulte , Purines/administration et posologie , Purines/effets indésirables , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Récepteurs à la progestérone/métabolisme , Préménopause , Survie sans progression , Kinase-4 cycline-dépendante/antagonistes et inhibiteurs
16.
Pol J Pathol ; 75(1): 8-18, 2024.
Article de Anglais | MEDLINE | ID: mdl-38741425

RÉSUMÉ

The use of chemotherapy in breast cancer management has significantly contributed to the decrease in its mortality. Currently, the prognosis is determined by molecular biomarkers, such as oestrogen receptors, and human epidermal growth factor receptor 2. However, the increasing use of advanced molecular technologies, including oncotype DX recurrence score (ODX-RS), has provided the ability to estimate the risk of recurrence. Research has demonstrated that the ODX-RS helps to predict recurrence risk and the potential benefit of chemotherapy in breast cancer. As a result, it can assist clinicians in making decisions regarding using the chemotherapy. The goal of work is to explore the correlation between the ODX-RS and Ki-67 proliferative index (Ki-67-PI). This study included 137 patients with oestrogen positive, human epidermal growth factor receptor 2-negative early breast cancer, and had non- or early axillary disease. Patients with low Ki-67-PI were as follows: low ODX-RS in 17%, intermediate ODX-RS in 80%, and high ODX-RS in 2%. In the high Ki-67-PI group: low ODX-RS in 12%, intermediate ODX-RS in 48%, and high ODX-RS in 40%. In conclusion, the results show no significant correlation between the ODX-RS and Ki-67-PI (r = 0.511, p-value < 0.9).


Sujet(s)
Marqueurs biologiques tumoraux , Tumeurs du sein , Antigène KI-67 , Récidive tumorale locale , Récepteur ErbB-2 , Récepteurs des oestrogènes , Humains , Tumeurs du sein/anatomopathologie , Femelle , Antigène KI-67/analyse , Récepteur ErbB-2/analyse , Récepteur ErbB-2/métabolisme , Adulte d'âge moyen , Marqueurs biologiques tumoraux/analyse , Adulte , Récidive tumorale locale/anatomopathologie , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Sujet âgé , Métastase lymphatique/anatomopathologie , Prolifération cellulaire , Aisselle , Récepteurs à la progestérone/métabolisme , Récepteurs à la progestérone/analyse , Sujet âgé de 80 ans ou plus
17.
Breast ; 76: 103739, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38754140

RÉSUMÉ

INTRODUCTION: Invasive lobular carcinoma (ILC) accounts for 5-15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile. METHODS: All patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile. RESULTS: A total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001). A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001). CONCLUSIONS: Atypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.


Sujet(s)
Tumeurs du sein , Carcinome lobulaire , Traitement néoadjuvant , Humains , Femelle , Carcinome lobulaire/anatomopathologie , Carcinome lobulaire/traitement médicamenteux , Carcinome lobulaire/mortalité , Tumeurs du sein/anatomopathologie , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/mortalité , Tumeurs du sein/thérapie , Adulte d'âge moyen , Sujet âgé , Adulte , Traitement médicamenteux adjuvant , Récepteur ErbB-2/métabolisme , Récepteur ErbB-2/analyse , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Marqueurs biologiques tumoraux/analyse , Résultat thérapeutique , Études rétrospectives , Survie sans rechute , Grading des tumeurs
18.
Breast ; 76: 103753, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38815444

RÉSUMÉ

BACKGROUND: Neoadjuvant chemotherapy (NACT) is widely used in the treatment of triple-negative and HER2-positive breast cancer (BC), but its use in estrogen receptor (ER) and/or progesterone receptor (PR) positive/HER2-negative BC is questioned because of the low pathologic complete response (pCR) rates. This retrospective study assessed the mRNA-based MammaTyper® assay's capability of predicting pCR with NACT, and ER, PR, Ki67, and HER2 status at immunohistochemical (IHC) through transcriptomics. METHODS: Diagnostic biopsies from 76 BC patients treated at the Cremona Hospital between 2012-2018 were analyzed. Relative mRNA expression levels of ERBB2, ESR1, PGR, and MKI67 were measured using the MammaTyper® kit and integrated into a pCR score. Predicting capability of pCR and standard IHC biomarkers could be assessed with ROC curves in 75 and 76 patients, respectively. RESULTS: Overall, 68.0% patients obtained a MammaTyper® high-score and 32.0% a MammaTyper® low-score. Among high-score patients, 62.7% achieved pCR, compared to 16.7% in the low-score group (p = 0.0003). The binary MammaTyper® score showed good prediction of pCR in the overall cohort (area under curve [AUC] = 0.756) and in HR+/HER2-negative cases (AUC = 0.774). In cases with residual disease, the continuous MammaTyper® score correlated moderately with residual tumor size and decrease in tumor size. MammaTyper® showed substantial agreement with IHC for ESR1/ER and ERBB2/HER2, and moderate agreement for PGR/PR and MKI67/Ki67. CONCLUSION: Overall, MammaTyper® pCR score may serve as a standardized tool for predicting NACT response in HR+/HER2-negative BC, potentially guiding treatment strategies. Additionally, it could provide a more standardized and reproducible assessment of ER, PR, HER2, and Ki67 status.


Sujet(s)
Marqueurs biologiques tumoraux , Tumeurs du sein , Traitement néoadjuvant , Récepteur ErbB-2 , Récepteurs des oestrogènes , Récepteurs à la progestérone , Humains , Femelle , Études rétrospectives , Adulte d'âge moyen , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/anatomopathologie , Tumeurs du sein/métabolisme , Récepteur ErbB-2/métabolisme , Récepteur ErbB-2/analyse , Adulte , Récepteurs à la progestérone/métabolisme , Récepteurs à la progestérone/analyse , Études transversales , Marqueurs biologiques tumoraux/analyse , Marqueurs biologiques tumoraux/métabolisme , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Sujet âgé , Traitement médicamenteux adjuvant , Antigène KI-67/analyse , Antigène KI-67/métabolisme , Immunohistochimie , Valeur prédictive des tests , Résultat thérapeutique , ARN messager/analyse , ARN messager/métabolisme , Courbe ROC
19.
Acta Oncol ; 63: 277-287, 2024 May 06.
Article de Anglais | MEDLINE | ID: mdl-38711384

RÉSUMÉ

BACKGROUND: Primary metastatic breast cancer (pMBC) accounts for 5-10% of annual breast cancers with a median survival of 3-4 years, varying among subtypes. In Denmark, the incidence of breast cancer increased until 2010, followed by a stabilisation. Several factors influencing pMBC incidence and survival, including screening prevalence, staging methods, and classification standards, remain pivotal but inadequately documented. MATERIAL AND METHOD: This retrospective observational study involving pMBC patients diagnosed between 2000 and 2020 encompassed all Danish oncology departments. Data from the Danish Breast Cancer Group database and the National Patient Register included diagnosis specifics, demographics, treatment, and follow-up. RESULTS: Between 2000 and 2020, 3,272 patients were diagnosed with pMBC, a rise from 355 patients in 2000-2004 to 1,323 patients in 2015-2020. The increase was particularly observed in patients aged 70 years or older. Changes in tumour subtypes were observed, notably with a rise in human epidermal growth factor receptor 2 (HER2)-positive cases but a steady distribution of estrogen receptor (ER) status. Diagnostic practices changed over the two decades, with 6% evaluated with PET/CT (positron emission tomography-computed tomography) or CT (computed tomography) with a bone evaluation in 2000-2004 and 65% in 2015-2020. Overall survival (OS) improved from 23 months in 2000-2004 to 33 months in 2015-2020. In patients with ER-positive and HER2-positive disease, the multivariable model showed improved survival by year of diagnosis, and further, patients with ER-negative/HER2-negative disease fared worse the first 2 years after diagnosis. INTERPRETATION: Our study delineates changes in the treatment and survival of pMBC over two decades. Stage migration, screening introduction, and changes in registration practice, however, prevent a valid assessment of a possible causal relationship.


Sujet(s)
Tumeurs du sein , Dépistage précoce du cancer , Stadification tumorale , Humains , Tumeurs du sein/anatomopathologie , Tumeurs du sein/mortalité , Tumeurs du sein/épidémiologie , Femelle , Danemark/épidémiologie , Sujet âgé , Études rétrospectives , Adulte d'âge moyen , Incidence , Adulte , Sujet âgé de 80 ans ou plus , Taux de survie , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Métastase tumorale , Tomographie par émission de positons couplée à la tomodensitométrie , Récepteur ErbB-2/métabolisme , Récepteur ErbB-2/analyse
20.
Breast ; 76: 103741, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38759576

RÉSUMÉ

BACKGROUND: The aim of this population-based cohort study was to investigate the impact of neoadjuvant chemotherapy (NACT) compared to adjuvant chemotherapy in prognosis among patients with HR+/HER2 negative breast cancer. METHOD: This population-based study utilized data from the research database BCBaSe 3.0, based on the Swedish National Quality breast cancer register, including all patients with breast cancer diagnosis in Sweden between 2008 and 2019. Propensity score matching approach was applied. The outcomes of interest consisted of distant-disease free (DDFS), breast-cancer specific (BCSS), and overall survival (OS). RESULTS: In total, 14 459 patients were included in the study cohort of whom 2086 received NACT. After 1:1 propensity score matching (PSM), 1539 patients in each study group were available for analyses. No statistically significant difference in survival outcomes were observed between patients treated with NACT compared to those treated with adjuvant chemotherapy (Hazard Ratio (HR) for DDFS: 1.20; 95 % CI: 0.80-1.79; HR for BCSS: 1.16; 95 % CI: 0.54-2.49; HR for OS: 1.14; 95 % CI: 0.64-2.05). CONCLUSION: In this population-based cohort study of patients with HR+/HER2-breast cancer, the use of NACT seems to be comparable to adjuvant chemotherapy in terms of prognosis, although non-inferiority cannot be proven by this study design. Until further evidence suggesting a survival benefit in favor of either treatment is available, NACT can be pursued when surgical-de-escalation is intended.


Sujet(s)
Tumeurs du sein , Traitement néoadjuvant , Score de propension , Récepteur ErbB-2 , Humains , Femelle , Traitement médicamenteux adjuvant , Tumeurs du sein/traitement médicamenteux , Tumeurs du sein/mortalité , Tumeurs du sein/métabolisme , Traitement néoadjuvant/statistiques et données numériques , Adulte d'âge moyen , Récepteur ErbB-2/métabolisme , Récepteur ErbB-2/analyse , Suède , Pronostic , Sujet âgé , Adulte , Récepteurs des oestrogènes/métabolisme , Récepteurs des oestrogènes/analyse , Études de cohortes , Récepteurs à la progestérone/métabolisme , Récepteurs à la progestérone/analyse , Survie sans rechute , Enregistrements
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