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1.
Int J Cancer ; 155(2): 339-351, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38554131

ABSTRACT

Tamoxifen prevents recurrence of breast cancer and is also approved for preventive, risk-reducing, therapy. Tamoxifen alters the breast tissue composition and decreases the mammographic density. We aimed to test if baseline breast tissue composition influences tamoxifen-associated density change. This biopsy-based study included 83 participants randomised to 6 months daily intake of placebo, 20, 10, 5, 2.5, or 1 mg tamoxifen. The study is nested within the double-blinded tamoxifen dose-determination trial Karolinska Mammography Project for Risk Prediction of Breast Cancer Intervention (KARISMA) Study. Ultrasound-guided core-needle breast biopsies were collected at baseline before starting treatment. Biopsies were quantified for epithelial, stromal, and adipose distributions, and epithelial and stromal expression of proliferation marker Ki67, oestrogen receptor (ER) and progesterone receptor (PR). Mammographic density was measured using STRATUS. We found that greater mammographic density at baseline was positively associated with stromal area and inversely associated with adipose area and stromal expression of ER. Premenopausal women had greater mammographic density and epithelial tissue, and expressed more epithelial Ki67, PR, and stromal PR, compared to postmenopausal women. In women treated with tamoxifen (1-20 mg), greater density decrease was associated with higher baseline density, epithelial Ki67, and stromal PR. Women who responded to tamoxifen with a density decrease had on average 17% higher baseline density and a 2.2-fold higher PR expression compared to non-responders. Our results indicate that features in the normal breast tissue before tamoxifen exposure influences the tamoxifen-associated density decrease, and that the age-associated difference in density change may be related to age-dependant differences in expression of Ki67 and PR.


Subject(s)
Antineoplastic Agents, Hormonal , Breast Density , Breast Neoplasms , Mammography , Tamoxifen , Humans , Tamoxifen/pharmacology , Tamoxifen/administration & dosage , Female , Breast Density/drug effects , Middle Aged , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/metabolism , Mammography/methods , Adult , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Double-Blind Method , Receptors, Estrogen/metabolism , Aged , Receptors, Progesterone/metabolism , Breast/drug effects , Breast/diagnostic imaging , Breast/pathology , Breast/metabolism , Ki-67 Antigen/metabolism , Ki-67 Antigen/analysis , Postmenopause
2.
N Engl J Med ; 385(5): 395-405, 2021 07 29.
Article in English | MEDLINE | ID: mdl-34320285

ABSTRACT

BACKGROUND: For postmenopausal women with hormone-receptor-positive breast cancer, the most effective duration for adjuvant therapy with an aromatase inhibitor remains unclear. METHODS: In this prospective, phase 3 trial, we randomly assigned postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy to receive the aromatase inhibitor anastrozole for an additional 2 years (2-year group, receiving a total of 7 years) or an additional 5 years (5-year group, receiving a total of 10 years). The primary end point was disease-free survival. The primary analysis included all the patients who were still participating in the trial and who had no recurrence 2 years after randomization (i.e., when treatment in the 2-year group had ended). Secondary end points were overall survival, contralateral breast cancer, second primary cancer, and clinical bone fracture. RESULTS: Among the 3484 women who were enrolled in the trial, 3208 remained in the trial without disease progression after the first 2 years of extended anastrozole treatment following randomization. Among these women, disease progression or death occurred in 335 women in each treatment group in the primary-analysis set at 8 years (hazard ratio, 0.99; 95% confidence interval [CI], 0.85 to 1.15; P = 0.90). No between-group differences occurred in most secondary end points, and subgroup analyses did not indicate differences in any particular subgroup. The risk of clinical bone fracture was higher in the 5-year group than in the 2-year group (hazard ratio, 1.35; 95% CI, 1.00 to 1.84). CONCLUSIONS: In postmenopausal women with hormone-receptor-positive breast cancer who had received 5 years of adjuvant endocrine therapy, extending hormone therapy by 5 years provided no benefit over a 2-year extension but was associated with a greater risk of bone fracture. (Funded by AstraZeneca and the Austrian Breast and Colorectal Cancer Study Group; ABCSG-16/SALSA ClinicalTrials.gov number, NCT00295620.).


Subject(s)
Anastrozole/administration & dosage , Aromatase Inhibitors/administration & dosage , Breast Neoplasms/drug therapy , Neoplasm Recurrence, Local/prevention & control , Administration, Oral , Aged , Anastrozole/adverse effects , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Aromatase Inhibitors/adverse effects , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Disease-Free Survival , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Humans , Kaplan-Meier Estimate , Middle Aged , Postmenopause , Prospective Studies , Receptors, Estrogen , Receptors, Progesterone , Tamoxifen/therapeutic use
3.
Breast Cancer Res Treat ; 206(3): 551-559, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38703285

ABSTRACT

PURPOSE: Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3 months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. METHODS: A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. RESULTS: One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15 months (interquartile range: 1-56 months). The median age at diagnosis was 49 years (range: 35-90 years). The estimated mPFS was 6.0 months (95%CI 5.3-7.8 months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18 months (8.7 months, 95%CI 6.6-11.3 months), in patients w/o visceral metastases (8.0 months, 95%CI 5.8-10.5 months), and chemotherapy-naïve in the metastatic setting (7.2 months, 95%CI 5.9-8.4 months). CONCLUSION: This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Breast Neoplasms , Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Everolimus , Receptor, ErbB-2 , Humans , Everolimus/administration & dosage , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Breast Neoplasms/mortality , Breast Neoplasms/metabolism , Middle Aged , Aged , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Adult , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Aged, 80 and over , Receptors, Progesterone/metabolism , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Tamoxifen/therapeutic use , Tamoxifen/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Aromatase Inhibitors/therapeutic use , Aromatase Inhibitors/administration & dosage , Fulvestrant/administration & dosage , Fulvestrant/therapeutic use , Progression-Free Survival , Androstadienes/administration & dosage , Androstadienes/therapeutic use , Disease Progression
4.
Curr Opin Oncol ; 36(6): 465-473, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39246179

ABSTRACT

PURPOSE OF REVIEW: Growth and survival of hormone receptor positive breast cancer cells are dependent on circulating hormones (e.g., estrogen and progesterone). Endocrine therapy improved outcomes in both early and advanced hormone receptor positive breast cancer. These treatments include drugs with different mechanisms of action, namely selective estrogen receptor modulators (SERM), aromatase inhibitors, and selective estrogen receptor degraders (SERDs). SERDs represent estrogen receptor antagonists, favoring its degradation and thus interfering with proliferation genes transcription and activation. Fulvestrant is the first approved SERD, administered intramuscularly for treating advanced breast cancer. RECENT FINDINGS: Oral SERDs have been tested to overcome the limitation of the intramuscular administration, and to increase SERD bioavailability. Recently, an oral SERD, Elacestrant, has been approved by the Food and Drug Administration (FDA) for patients carrying an ESR1 mutation. In fact, oral SERDs seem to be effective in tumors harboring ESR1 mutations, a well known mechanism of resistance to endocrine therapy (especially aromatase inhibitors). SUMMARY: More recently, oral SERDs have been tested in patients with early hormone receptor positive breast cancer, although their impact on survival and in this curative setting compared to standard endocrine therapy still needs to be elucidated. The best timing and duration of SERD administration and specific biomarkers in (neo)adjuvant setting remain largely unknown.


Subject(s)
Antineoplastic Agents, Hormonal , Breast Neoplasms , Selective Estrogen Receptor Modulators , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Selective Estrogen Receptor Modulators/therapeutic use , Selective Estrogen Receptor Modulators/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Administration, Oral , Aromatase Inhibitors/therapeutic use , Aromatase Inhibitors/administration & dosage
5.
Eur J Clin Pharmacol ; 80(9): 1387-1397, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38900307

ABSTRACT

PURPOSE: The aim of this study was to quantitatively compare the efficacy and safety of CDK4/6 inhibitors and PI3K/AKT/mTOR inhibitors for ER+/HER2- metastatic breast cancer. METHODS: A parametric survival function was used to analyze the time course of overall survival (OS) and progression-free survival (PFS). The objective response rate (ORR) and the incidence of any grade and grade 3-4 adverse events were summarized using the random-effects model of a single-arm meta-analysis. RESULTS: This study included 44 arms from 48 publications, with a total sample size of 7881 patients. Our study revealed that CDK4/6 inhibitors had a median OS of 40.7 months, a median PFS of 14.8 months, and an ORR of 40%, whereas PI3K/AKT/mTOR inhibitors had a median OS of 29.8 months, a median PFS of 8.3 months, and an ORR of 20%. Additionally, this study also found that the proportion of patients with visceral metastases and specific endocrine therapy used in combination significantly impact OS and PFS. In terms of adverse events, CDK4/6 inhibitors exhibited a relatively high incidence of hematological adverse events. CONCLUSION: Our study provides solid quantitative evidence for the first-line recommendation of CDK4/6 inhibitors combined with endocrine therapy for ER+/HER2- metastatic breast cancer in clinical guidelines.


Subject(s)
Breast Neoplasms , Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Receptor, ErbB-2 , Humans , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Receptor, ErbB-2/metabolism , Receptor, ErbB-2/antagonists & inhibitors , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Cyclin-Dependent Kinase 6/antagonists & inhibitors , TOR Serine-Threonine Kinases/antagonists & inhibitors , Receptors, Estrogen/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/administration & dosage , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/metabolism , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Phosphoinositide-3 Kinase Inhibitors/administration & dosage , Progression-Free Survival , Neoplasm Metastasis
6.
Future Oncol ; 20(28): 2037-2048, 2024.
Article in English | MEDLINE | ID: mdl-39023253

ABSTRACT

WHAT IS THIS SUMMARY ABOUT?: This article summarizes the most recent results of the monarchE study. This study was completed in participants with a type of breast cancer called HR+, HER2-, node-positive, high-risk early breast cancer. In this study, abemaciclib, a non-chemotherapy treatment, was administered with standard of care endocrine therapy after curative surgery. Most participants had received prior chemotherapy and/or radiotherapy. The study investigated if abemaciclib helped participants live longer without their cancer returning compared with participants who only received standard of care endocrine therapy. The study participants were assigned to 1 of 2 treatment groups. Participants in Group A were assigned to receive standard of care endocrine therapy with abemaciclib for 2 years, followed by endocrine therapy for a total of at least 5 years. Participants in Group B were assigned to receive standard of care endocrine therapy only for at least 5 years. The effect of treatment was compared between these 2 groups. WHAT WERE THE RESULTS?: Overall, the results showed that the cancer was 34% less likely to come back after surgery in the participants in Group A (abemaciclib plus endocrine therapy) compared with those in Group B (endocrine therapy only). At 4 years since the start of the study treatment, more participants who received the combination of abemaciclib plus endocrine therapy remained free of cancer compared with participants who received endocrine therapy alone (86% versus 79%). Participants who received abemaciclib plus endocrine therapy had more side effects than those who received endocrine therapy alone, but most of these effects were mild to moderate and reversible upon the end of therapy. The most common side effects in the abemaciclib group were diarrhea, infections, low number of white blood cells, and tiredness. WHAT DO THE RESULTS MEAN?: This study found that administering abemaciclib in combination with standard endocrine therapy after curative breast surgery helped lower the risk of cancer returning in people with HR+, HER2-, node-positive, high-risk early breast cancer. Abemaciclib is a new treatment option for people with this diagnosis. People with high-risk early breast cancer should always talk to their doctors and nurses before making any decisions about their treatment.Clinical Trial Registration: NCT03155997 (monarchE study).


Subject(s)
Aminopyridines , Antineoplastic Combined Chemotherapy Protocols , Benzimidazoles , Breast Neoplasms , Receptor, ErbB-2 , Humans , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/therapy , Female , Benzimidazoles/administration & dosage , Benzimidazoles/therapeutic use , Aminopyridines/administration & dosage , Aminopyridines/therapeutic use , Receptor, ErbB-2/metabolism , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Receptors, Estrogen/metabolism , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Middle Aged , Receptors, Progesterone/metabolism , Adult , Treatment Outcome , Aged , Neoplasm Staging
7.
Int J Gynecol Cancer ; 34(8): 1217-1224, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38724237

ABSTRACT

OBJECTIVE: This study aimed to evaluate fulvestrant efficacy in women with estrogen receptor-positive low-grade gynecological cancers. The primary objective was to determine the response rate. Secondary objectives were progression-free survival, clinical benefit, duration of response, safety, tolerability, and quality of life. METHODS: FUCHSia is an open-label, single-arm, prospective, multi-center phase II study. The study population included patients with recurrent/metastatic low-grade gynecological malignancies with estrogen receptor positivity who received a maximum of two lines of previous hormonal therapy. Patients received fulvestrant (FASLODEX, AstraZeneca) via two intramuscular injections (250 mg/5 mL each) in the gluteal muscle on day 1, day 15, day 29, and then every 28 days thereafter until disease progression, withdrawal from the trial due to any unacceptable adverse event, or withdrawal of patient consent. RESULTS: A total of 15 patients (uterine sarcoma n=4; sex cord-stromal ovarian tumors n=3; endometrial carcinoma n=4; serous ovarian cancer n=4) were enrolled. Median follow-up was 48 weeks (interquartile range (IQR) 26-122) in the uterine sarcoma cohort, 63 weeks (IQR 28-77) for sex cord-stromal tumors, 19 weeks (IQR 17-21) for endometrial carcinoma, and 60 weeks (IQR 40-119) for serous ovarian cancer. One partial response according to Response Evaluation Criteria in Solid Tumors v1.1 was observed in one uterine sarcoma patient. No responses were observed in the other cohorts. However, stable disease was observed in three uterine sarcomas (median duration 12 weeks), three sex cord-stromal tumors (median duration 32 weeks), and four low-grade serous ovarian cancer patients (median duration 20 weeks), leading to a disease control rate of 100% for these tumor types. All patients with endometrial carcinoma showed progressive disease. CONCLUSION: Fulvestrant may control tumor growth in recurrent/metastatic estrogen receptor-positive low-grade gynecological malignancies of specific histology. Further studies are needed to confirm these results.


Subject(s)
Fulvestrant , Neoplasm Recurrence, Local , Receptors, Estrogen , Humans , Female , Middle Aged , Prospective Studies , Fulvestrant/administration & dosage , Fulvestrant/therapeutic use , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/metabolism , Adult , Aged , Receptors, Estrogen/metabolism , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Genital Neoplasms, Female/drug therapy , Genital Neoplasms, Female/pathology , Genital Neoplasms, Female/metabolism , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Sex Cord-Gonadal Stromal Tumors/drug therapy , Sex Cord-Gonadal Stromal Tumors/pathology
8.
Postgrad Med J ; 100(1188): 703-708, 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-38767468

ABSTRACT

For metastatic prostate cancer, androgen deprivation therapy (ADT) is the key strategy to control the disease. However, after 18-24 months of treatment, most patients will progress from metastatic hormone-sensitive prostate cancer (mHSPC) to metastatic castration-resistant prostate cancer (mCRPC) even with ADT. Once patients enter into mCRPC, they face with significant declines in quality of life and a dramatically reduced survival period. Thus, doublet therapy, which combines ADT with new hormone therapy (NHT) or ADT with docetaxel chemotherapy, substitutes ADT alone and has become the "gold standard" for the treatment of mHSPC. In recent years, triplet therapy, which combines ADT with NHT and docetaxel chemotherapy, has also achieved impressive effects in mHSPC. This article provides a comprehensive review of the recent applications of the triplet therapy in the field of mHSPC.


Subject(s)
Androgen Antagonists , Antineoplastic Combined Chemotherapy Protocols , Docetaxel , Prostatic Neoplasms , Humans , Male , Androgen Antagonists/therapeutic use , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Docetaxel/therapeutic use , Docetaxel/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Quality of Life , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Neoplasm Metastasis
9.
World J Surg Oncol ; 22(1): 169, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918837

ABSTRACT

OBJECTIVE: This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility. METHODS: Our study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3-4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy. RESULTS: Overall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages. CONCLUSION: GnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.


Subject(s)
Drug Resistance, Neoplasm , Endometrial Hyperplasia , Endometrial Neoplasms , Fertility Preservation , Progestins , Humans , Female , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Adult , Retrospective Studies , Fertility Preservation/methods , Endometrial Hyperplasia/drug therapy , Endometrial Hyperplasia/pathology , Progestins/administration & dosage , Progestins/therapeutic use , Follow-Up Studies , Pregnancy , Drug Resistance, Neoplasm/drug effects , Gonadotropin-Releasing Hormone/agonists , Levonorgestrel/administration & dosage , Middle Aged , Prognosis , Intrauterine Devices, Medicated , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Pregnancy Rate , Aromatase Inhibitors/therapeutic use , Aromatase Inhibitors/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage
10.
J Obstet Gynaecol Res ; 50(9): 1614-1621, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39092804

ABSTRACT

AIMS: To evaluate the safety and effectiveness of high-dose oral medroxyprogesterone acetate (MPA) therapy as a fertility-sparing treatment for patients diagnosed with atypical endometrial hyperplasia (AEH) and endometrioid carcinoma G1 without myometrial invasion (G1EC). Particular attention was given to the extended administration and readministration of MPA for patients with persistent disease following initial treatment and those with recurrence. METHODS: We conducted a retrospective analysis of data from 79 patients who underwent daily oral MPA treatment between 2005 and 2024 at Nagoya University Hospital. Patient characteristics, treatment outcomes, factors contributing to recurrence, and post-MPA therapy pregnancies were examined. RESULTS: MPA therapy achieved a remarkable complete response (CR) rate of 91.1%. The median time to achieve CR was 26.0 and 40.0 weeks for AEH and G1EC patients, respectively. Importantly, 27 patients (39.7%) attained CR after more than 6 months of treatment, including 8 patients (11.8%) who achieved CR after more than a year of treatment. The recurrence rates were 52.9% for AEH and 64.7% for G1EC. Twenty eight patients resumed MPA treatment, and 23 achieved second CR. Notably, recurrence was not associated with clinical factors such as age, body mass index, or post-CR pregnancy. Among patients who attempted pregnancy after achieving CR, 22 live births were successfully achieved. CONCLUSIONS: High-dose oral MPA therapy demonstrated both safety and efficacy for preserving fertility in patients with AEH and G1EC, resulting in a high CR rate. MPA extension and readministration proved to be beneficial strategies for managing patients with recurrence and persistent disease following initial treatment.


Subject(s)
Endometrial Hyperplasia , Endometrial Neoplasms , Fertility Preservation , Medroxyprogesterone Acetate , Humans , Female , Medroxyprogesterone Acetate/administration & dosage , Medroxyprogesterone Acetate/therapeutic use , Endometrial Hyperplasia/drug therapy , Adult , Endometrial Neoplasms/drug therapy , Retrospective Studies , Pregnancy , Fertility Preservation/methods , Carcinoma, Endometrioid/drug therapy , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Middle Aged , Treatment Outcome
11.
J Avian Med Surg ; 38(3): 153-161, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39405214

ABSTRACT

An intracoelomic mass was palpated on an annual exam of a 24-year-old male Solomon Island eclectus parrot (Eclectus roratus solomonensis). The initial diagnostic workup included a complete blood count, plasma biochemistry panel, and coelomic ultrasound. Computed tomography was highly suggestive of a testicular mass. Tamoxifen and the gonadotropin-releasing hormone agonists leuprolide and deslorelin were administered as neoadjunctive endocrine therapies. Biopsy and histologic examination confirmed a testicular mass consistent with a round cell tumor. Four doses of carboplatin 15 mg/kg IV were administered as neoadjunctive chemotherapy, and testicular size decreased by approximately 95%. The remaining gross tumor was removed via orchidectomy with clean but narrow margins. Seven months following surgery, a contrast CT scan did not show any evidence of recurrence of or metastasis from the original mass. This is the first report of successful treatment of a testicular tumor in a psittacine with neoadjuvant chemotherapy and orchidectomy.


Subject(s)
Bird Diseases , Neoadjuvant Therapy , Parrots , Testicular Neoplasms , Male , Animals , Testicular Neoplasms/veterinary , Testicular Neoplasms/drug therapy , Testicular Neoplasms/pathology , Testicular Neoplasms/surgery , Bird Diseases/drug therapy , Bird Diseases/pathology , Bird Diseases/surgery , Neoadjuvant Therapy/veterinary , Orchiectomy/veterinary , Triptorelin Pamoate/administration & dosage , Triptorelin Pamoate/analogs & derivatives , Triptorelin Pamoate/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Leuprolide/therapeutic use , Leuprolide/administration & dosage , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Tamoxifen/therapeutic use , Tamoxifen/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage
12.
Gan To Kagaku Ryoho ; 51(6): 651-653, 2024 Jun.
Article in Japanese | MEDLINE | ID: mdl-39009524

ABSTRACT

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.


Subject(s)
Breast Neoplasms , Ethinyl Estradiol , Recurrence , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/therapeutic use , Aged, 80 and over , Receptors, Estrogen/analysis , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Receptors, Progesterone/metabolism
13.
Gynecol Oncol ; 174: 106-113, 2023 07.
Article in English | MEDLINE | ID: mdl-37172410

ABSTRACT

OBJECTIVES: To evaluate oncologic and pregnancy outcomes of fertility-sparing treatment (FST) using progestin in patients with stage I grade 2 endometrioid endometrial cancer (EC) without myometrial invasion (MI) or grade 1-2 with superficial MI. METHODS: Multicenter data of patients with stage I grade 2 EC without MI or grade 1-2 EC with superficial MI, who received FST between 2005 and 2021, were analyzed. Cox regression analysis identified independent factors for progressive disease (PD) during the FST. RESULTS: Altogether, 54 patients received FST [medroxyprogesterone acetate (500-1000 mg) in 44, megestrol acetate (40-800 mg) in 10] with concurrent levonorgestrel-releasing intrauterine devices use in 31. With median time to achieve a complete response (CR) of 10 (3-24) months, 39 patients (72.2%) achieved CR. Of the 15 patients who attempted to conceive after achieving CR, 7 (46.7%) became pregnant (2 abortions, 5 live births). During a median FST duration of 6 (3-12) months, nine patients (16.6%) were diagnosed with PD. Fifteen (38.5%) experienced recurrence with a median recurrence-free survival of 23 (3-101) months. In the multivariable analysis, tumor size before FST ≥2 cm (HR 5.456, 95% CI 1.34 to 22.14; p = 0.018) was significantly associated with a high PD rate during FST. CONCLUSION: The overall response rate to FST was promising, however, the PD rate was significant during the first 12 months of FST. Therefore, performing thorough endometrial biopsy and imaging studies is essential to strictly evaluate the extent of the disease every 3 months from FST initiation.


Subject(s)
Endometrial Neoplasms , Fertility Preservation , Female , Humans , Pregnancy , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/therapeutic use , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/pathology , Fertility Preservation/methods , Proportional Hazards Models , Retrospective Studies , Treatment Outcome , Progestins/administration & dosage , Progestins/therapeutic use , Disease Progression , Neoplasm Staging , Adolescent , Young Adult , Adult , Biopsy
18.
Neuroendocrinology ; 112(1): 88-100, 2022.
Article in English | MEDLINE | ID: mdl-33508849

ABSTRACT

INTRODUCTION: Somatostatin analogs (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NENs. METHODS: We identified patients with well-differentiated (Ki-67% ≤20%), metastatic GEP-NENs treated in first line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real-world clinical practice versus RCTs. RESULTS: The dataset contained 535 patients with a median age of 62 years (range: 26-89). The median Ki-67% was 4 (range: 0-20). The most common primary tumor sites were as follows: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n = 266) and half, lanreotide autogel (n = 269). The median PFS was 28.0 months (95% CI: 22.1-32.0) for octreotide versus 30.1 months (95% CI: 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide versus octreotide was 0.90 (95% credible interval: 0.71-1.12). The probability of effect sizes >30% with lanreotide versus octreotide was 2 and 6% for midgut and foregut NENs, respectively. CONCLUSION: Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data). Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.


Subject(s)
Antineoplastic Agents, Hormonal/pharmacology , Intestinal Neoplasms/drug therapy , Neuroendocrine Tumors/drug therapy , Octreotide/pharmacology , Pancreatic Neoplasms/drug therapy , Peptides, Cyclic/pharmacology , Progression-Free Survival , Randomized Controlled Trials as Topic/standards , Registries , Somatostatin/analogs & derivatives , Somatostatin/analysis , Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Hormonal/administration & dosage , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Octreotide/administration & dosage , Peptides, Cyclic/administration & dosage , Prognosis , Reproducibility of Results , Somatostatin/administration & dosage , Somatostatin/pharmacology , Spain
19.
Future Oncol ; 18(21): 2575-2584, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35587650

ABSTRACT

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a research study (known as a clinical trial) called HERO. The HERO study compared how well relugolix and leuprolide worked in lowering blood testosterone to sustained castration levels in men with advanced prostate cancer. Sustained castration is a blood testosterone level below 50 ng/dl from Day 29 through 48 weeks of treatment. WHAT WERE THE RESULTS?: Researchers looked at 930 adult men with advanced prostate cancer: 622 of these men took relugolix (by mouth once daily) and 308 received leuprolide (injected every 3 months). The HERO study showed that more men taking relugolix (97%) achieved sustained castration through 48 weeks than men receiving leuprolide (89%). This decrease in testosterone also happened more quickly in men taking relugolix. In 184 men who were followed up for 90 days after completing treatment, blood levels of testosterone returned to normal in more men who took relugolix than men who received leuprolide. Side effects were similar among men taking relugolix or receiving leuprolide, and most were identified as mild or moderate in terms of how bad they were. WHAT DO THE RESULTS OF THE STUDY MEAN?: In men with advanced prostate cancer and compared with those receiving leuprolide, more men taking relugolix had lower levels of blood testosterone. ClinicalTrials.gov NCT number: NCT03085095.


Subject(s)
Melanoma , Prostatic Neoplasms , Adult , Antibodies, Monoclonal, Humanized , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Hormonal/adverse effects , Humans , Ipilimumab/therapeutic use , Language , Leuprolide/administration & dosage , Leuprolide/adverse effects , Male , Melanoma/drug therapy , Phenylurea Compounds , Prostatic Neoplasms/blood , Prostatic Neoplasms/drug therapy , Pyrimidinones , Testosterone/blood
20.
Acta Med Okayama ; 76(1): 17-24, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35236994

ABSTRACT

R-CHOP therapy is generally performed every 3 weeks. We investigated the effects of extending the interval of R-CHOP therapy for > 1 week on the prognoses of patients with non-indolent non-Hodgkin's B-cell lymphoma. Among the 338 patients with non-indolent non-Hodgkin's B-cell lymphoma who received initial chemotherapy at our institution, we focused on 178 patients who received R-CHOP therapy and analyzed the outcomes of the patients stratified by the treatment intervals. The estimated 3-year overall survival (OS) for the entire population was 82.1%. Patients treated at intervals of ≥ 4 weeks were significantly older, and they had significantly longer follow-up periods and lower relative dose intensity. But the estimated 3-year OS was comparable to those treated at <4 weeks (83.3% vs. 80.5% p=0.947). In a multivariate analysis, age and the dose of anti-cancer agents had significant impacts on OS, but there was no significant relationship regarding the treatment intervals. Propensity score matching confirmed the same result. R-CHOP therapy every around 4 weeks could achieve relatively good survival in some selected patients with non-indolent non-Hodgkin's B-cell lymphoma.


Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, B-Cell/drug therapy , Aged , Cyclophosphamide/administration & dosage , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Humans , Male , Middle Aged , Prednisone/administration & dosage , Prognosis , Retrospective Studies , Rituximab/administration & dosage , Vincristine/administration & dosage
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