Genitourinary syndrome of menopause in patients with breast cancer treated by hormonotherapy: women's perception in ITAC, a French web-based survey.

OBJECTIVE: To describe frequency, intensity and impact of genito-urinary syndrome of menopause (GUSM) in breast cancer (BC) survivors receiving hormonotherapy (HT). METHODS: Web-based survey hosted on the Seintinelles website (database of patients and caregivers). Specific questionnaire of 43 questions, including sociodemographic characteristics, history of BC, characteristics of HT, side effects other than GUSM, symptoms of GUSM (frequency, intensity, treatment, and impact) and overall expectations regarding treatment. RESULTS: Among 1157 participants, 96.4% had at least one GUSM symptom. Percentages with at least one urinary, gynecological, or sexual symptom were 56.0%, 85.6% and 86.1% respectively while 70.3% and 10% declared at least 5 and 10 symptoms respectively. Mean (SD) and median (range) numbers of symptoms were 5.9 (2.8) and 6 (0-14) respectively. Most frequently reported symptoms were decreased desire (77.8%), decreased arousal (71.4%), and vaginal dryness 68.4%). On a scale from 0 (no impact) to 10 (maximal impact), the most important impact was reported for sexual life (mean: 6.6±3.5) followed by psychological condition/self-image (mean 5.4±3.1), and relations with partners (mean: 5.1±3.4). Only 13.6% of participants had received information on GUSM prior to the survey. CONCLUSIONS: GUSM remains underdiagnosed and underestimated in BC survivors who receive HT, although it is among most frequent and disabling side effects of HT. Awareness should be increased among physicians, along with information to women. Early detection and treatment of symptoms and prophylaxis of GUSM in at-risk women should be implemented.

Recalcitrant Paraneoplastic Pemphigus Associated With Prostate Adenocarcinoma: Spectacular Evolution Under Androgen Deprivation.

Paraneoplastic pemphigus (PNP) is a rare, autoimmune, blistering condition defined by severe stomatitis, polymorphous cutaneous eruptions, and underlying neoplasms. PNP associated with solid cancer is extremely rare. An association with prostate adenocarcinoma remains exceptional. We describe a 69-year-old patient with recalcitrant PNP associated with prostate adenocarcinoma showing spectacular response immediately after associating hormonotherapy with conventional immunosuppressive drugs.

[Venous thromboembolism and breast cancer]. / Maladie thromboembolique veineuse et cancer du sein.

Breast cancer is the most common cancer in women. Patients with breast cancer have a 4-fold increased risk of venous thromboembolism (VTE) compared to age- and sex-matched controls without cancer. VTE remains the second leading cause of death in cancer patients and an independent risk factor for mortality. In women with breast cancer, the main risk factors for developing VTE are increasing age, obesity, disease stage, central catheter placement and cancer treatments, including surgery, chemotherapy, hormonotherapy and cyclin-dependent kinase 4/6 inhibitors. In women receiving tamoxifen, the risk of VTE is particularly increased within the first 6 months after initiation of hormonotherapy, although some evidence suggests that this risk may persist through the first 2 years of treatment. The risk of VTE appears to be lower in patients receiving aromatase inhibitors. In breast cancer patients receiving cyclin-dependent kinase 4/6 inhibitors, the rate of VTE is approximately 6%. Current clinical practice guidelines for the treatment and prevention of VTE in patients with cancer suggest that thromboprophylaxis should not be used routinely in ambulatory cancer patients receiving chemotherapy or hormonotherapy. The risk-benefit ratio of thromboprophylaxis should be assessed on a case-by-case basis and be the subject of multidisciplinary discussion.

[Endometrial stromal sarcoma: French Guidelines from the French Sarcoma Group and the Rare Malignant Gynecologic Tumors Group]. / Sarcomes du stroma endométrial de bas grade : référentiels de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG.

Low-grade endometrial stromal sarcoma (LG-ESS) accounts for approximately 15% of all uterine sarcomas. Median age of patients is around 50 years and half of the patients are premenopausal. In all, 60% of cases present with FIGO stage I disease. Preoperatively radiologic findings of ESS are not specific. Pathological diagnosis remains essential. This review aimed to present the French guidelines for low grade ESS treatment within the Groupe sarcome français - Groupe d'étude des tumeurs osseuse (GSF-GETO)/NETSARC+ and tumeur maligne rare gynécologique (TMRG) networks. Treatments should be validated in multidisciplinary team involved in sarcomas or rare gynecologic tumors. Hysterectomy is the cornerstone of treatment for localized ESS, and morcellation should be avoided. Systematic lymphadenectomy in ESS does not improve the outcome and is not recommended. Leaving the ovaries in situ in stage I tumors could be discussed for young women. Adjuvant hormonal treatment could be considered, for two years for stage I with morcellation or stage II and livelong for stages III or IV. Nevertheless, several questions remain, such as optimal doses, regimens (progestins or aromatase inhibitors) and duration of therapy. Tamoxifen is contraindicated. Secondary cytoreductive surgery if feasible for recurrent disease, appears to be an acceptable approach. Systemic treatment for recurrent or metastatic disease is mainly hormonal, with or without surgery.

The Close Relationship Between Metabolic Syndrome and Hormone Receptor-Positive Early-Stage Breast Cancer.

OBJECTIVE: The primary aim of the current study was to investigate the frequency of metabolic syndrome (MS) in early-stage breast cancer patients. Additionally, clinicopathological factors, such as anthropometric measurements and hormonotherapy, were examined for their roles as potential confounders of MS in these patients. PATIENTS AND METHODS: In this retrospective cross-sectional study, all patients diagnosed with early breast cancer were included. Patients were divided into 2 groups with respect to MS diagnosis. Peripheral blood samples were obtained, clinical data were recorded, and body mass index (BMI) was calculated. RESULTS: The study was completed with a total of 207 patients of which 128 (61.8%) had MS. MS was more frequent hormone receptor positive subgroup and in recipients of adjuvant hormonotherapy. The comparison of patients with and without MS revealed significant differences in age, BMI and estrogen/progesterone receptor status. There were no significant differences between groups in terms of cancer stage, inflammatory markers, basal insulin and LDL levels, and tumor markers. CONCLUSION: MS appears to be rather widespread among women with early-stage breast cancer, and lifestyle changes, which can improve obesity-related adverse outcomes, should be more emphasized in clinical practice.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

Paradigm change in urological, gynaecological and breast cancer management: A new practice-changing data from ASCO 2022 annual meeting.

Changing medical practice has been a constant process based on many scientific findings for years. In the oncology community, the American Society of Clinical Oncology (ASCO), one of the major annual conferences, presented the latest updates on practice-changing in cancer. At the recent meeting of 2022, held this year on June 2-6, researchers presented essential findings in urological, gynecological, and breast cancer management. In urological cancer, olaparib + abiraterone was demonstrated thru the PROpel trial to benefit in first-line treatment mCRPC regardless of the HRR stratification factor, along with the adjuvant therapy everolimus, for fully resected RCC in the EVEREST trial. In gynecological cancer, tisotumab vedotin demonstrated a potential role in improving clinical outcomes in 1st line r/mCC thru InnovaTV-205. In breast cancer, trastuzumab deruxtecan showed significant benefit for redefined human epidermal growth factors receptor 2 status in HER2 low BC patients, where current targeted-HER2 therapies are ineffective in the DESTINY-BREAST 04 study. The use of Immuno-based combinations in the medical management of TNBC patients has been supported thru several recent studies, showing positive results and outcomes, as demonstrated by the expert's opinions in Rizzo et al. research papers. In this article, we resumed the different renowned and what we considered intriguing to review studies presented during these three long sessions at the ASCO 2022 meeting.

[Impact of adapted physical activity on joint pain induced under adjuvant hormone therapy for breast cancer: A review of the literature]. / Impact de l'activité physique adaptée sur les douleurs articulaires induites sous hormonothérapie adjuvante du cancer du sein : une revue de la littérature.

Hormone therapy provides an excellent survival rate after cancer but has many side effects, including joint pain in one out of two women. This leads about 13 % of women to stop their treatment within the first 6 months, impacting on its effectiveness, survival and the risk of recurrence. In order to better manage pain and quality of life, physical activity is highly recommended. In this context, the present review proposes a state of the art on the effects of adapted physical activity, based on the works referenced in PubMed. These studies show that physical activity has proved its worth in the primary prevention of cancer and is being evaluated in secondary prevention, particularly in the reduction of adverse effects. Overall, there is a reduction in joint pain, an improvement in quality of life and fatigue. Physical activity also plays a role in tertiary prevention. Paradoxically, oncologists and educators often note a reduction in the practice of physical activity due to fear of the onset of pain. It seems necessary to reinforce communication with patients and health professionals and to recommend the practice of physical activity in an appropriate setting.

Effects of the intestinal microbiota on prostate cancer treatment by androgen deprivation therapy.

Prostate cancer (PC) can be kept in check by androgen deprivation therapy (ADT, usually with the androgen synthesis inhibitor abiraterone acetate or the androgen receptor antagonist such as enzalutamide) until the tumor evolves to castration-resistant prostate cancer (CRPC). The transition of hormone-sensitive PC (HSPC) to CPRC has been explained by cancer cell-intrinsic resistance mechanisms. Recent data indicate that this transition is also marked by cancer cell-extrinsic mechanisms such as the failure of ADT-induced PC immunosurveillance, which depends on the presence of immunostimulatory bacteria in the gut. Moreover, intestinal bacteria that degrade drugs used for ADT, as well as bacteria that produce androgens, can interfere with the efficacy of ADT. Thus, specific bacteria in the gut serve as a source of testosterone, which accelerates prostate cancer progression, and men with CRPC exhibit an increased abundance of such bacteria with androgenic functions. In conclusion, the response of PC to ADT is profoundly influenced by the composition of the microbiota with its immunostimulatory, immunosuppressive and directly ADT-subversive elements.

Hormonal Therapy in Pretreated Patients With Recurrent Ovary Granulosa Cell Tumor.

Objective: To evaluate the effectiveness of hormonal therapy (HT) in patients with recurrent adult ovary granulosa cell tumors. Methods: The clinical and treatments features of the patients who received HT were studied retrospectively. The efficacy and safety of HT were evaluated. The Kaplan-Meier technique was used to conduct survival analysis. Results: The research involved a total of thirteen patients. The median age of the participants was 49 years (range: 34-61). Since diagnosis, the median number of surgeries has been three (range: 2-8). At least one chemotherapy regimen has been administered to 12 (92.3%) patients. Ten of the patients (76.9%) had at least two metastatic areas. Lung metastases were found in two (15.4%) of the patients. Inhibin B levels were elevated in 81.2% of patients before hormone treatment. The patients received different HTs (Leuprolide acetate + anastrozole-three patients, leuprolide acetate + tamoxifen-six patients, only anastrozole-three patients, only tamoxifen-one patients). The median progression-free survival was found 17.7 months (95 % CI: 14.7-20.6). In four (33.4%) patients, an overall response (complete or partial) was identified. A stable response was observed in eight (66.7%) patients. Conclusions: HT is effective in pretreated individuals with recurrent ovarian granulosa cell tumors, according to this research. Despite the limited number of patients and treatment variability, disease control was achieved in all patients. Also, we found that Inhibin B levels were associated with treatment response.

Arrabidaea chica chloroform extract modulates estrogen and androgen receptors on luminal breast cancer cells.

BACKGROUND: Breast Cancer (BC) is the most common cancer in women worldwide and, although 70% of patients are responsive to selective Estrogen Receptor (ER) modulators such as Tamoxifen (Tam), patients' survival is comprised by resistance to endocrine therapy. Brazilian flora, especially the Amazon biome, is one of the richest global sources of native species with potentially bioactive compounds. Arrabidaea chica is a plant native to the Amazon that has been used in the treatment of different diseases. However, its action on BC remains unclear. METHODS: Herein the biological effects of the chloroform extract of A. chica (CEAC) were evaluated on BC cells and in in vivo model. After confirmation of CEAC antioxidant capacity, cells were treated with CEAC and Tam, alone and with CEAC+Tam. The cell viability was evaluated by MTT and hormone receptor transcripts levels were assessed (ESR1, ESR2 and AR). Finally, anticarcinogenicity of CEAC was recorded in Drosophila melanogaster through Epithelial Tumor Test (ETT). RESULTS: The study confirmed the antioxidant activity of CEAC. CEAC was selective for MCF-7, downregulating ESR2 and AR transcripts and upregulating ESR2 expression. The modulatory effects of CEAC on ERs did not differ between cells treated with Tam and with CEAC+Tam. Interestingly, previous treatment with CEAC, followed by treatment with Tam promoted a significant decrease in cell viability. The extract also presented anticarcinogenic effect in in vivo assay. CONCLUSION: The bioassays on breast tumor cells demonstrated the antiproliferative activity of the extract, which modulated the expression of hormone receptors and sensitized luminal tumor cells to Tam. These results suggest that CEAC could be a complementary treatment for BC.

Elacestrant in metastatic breast cancer: Is the "standard of care" meeting standard requirements?

The EMERALD trial was an open label phase 3 trial evaluating elacestrant, the first oral selective estrogen receptor degrader (SERD), as compared to "standard of care", in ER+/HER2- (hormone receptor positive, no HER2 overexpression) advanced or metastatic breast cancer. The EMERALD trial restricted the "standard of care" control arm to limited options that may have led to a substandard control arm. We describe how the EMERALD trial protocol allowed different clinically inappropriate scenarios in the control arm, according to prior therapy. The main relevant question remains the potential advantage of elacestrant over fulvestrant in fulvestrant-naive patients. Analyzing outcomes in subgroups according to prior and per-protocol therapy would help analyzing trial results. However, these subgroup results may be non-significant, and another randomized trial will be needed. Trials should be designed to answer directly clinical questions that are relevant.

Primary ectopic axillary breast cancer: a case series.

INTRODUCTION: Ectopic breast tissue is present in 2-6% of women. Ectopic breast cancer represents an uncommon disease accounting for about 0.3% of all breast neoplasms, limiting the available evidence. Thus, we aim to report long-term outcomes in five cases treated at our institution. CASE SERIES: Our Tunisian patients' median age was 48 years (33-60 years), and the median follow-up was 8 years (4-10 years). The ectopic breast tissue was located four times in the right axilla. The median tumor size was 25 mm (15-55 mm). Four of the patients underwent a wide local excision and axillary lymph node dissection. Three of those women had positive lymph nodes; thus, they received adjuvant chemotherapy, radiation therapy, and hormone therapy. The patient with a negative lymph node (case 5) had adjuvant radiation therapy and hormonal therapy. One of the patients (case 1) had a positive supraclavicular lymph node and received radiation therapy, chemotherapy, and hormonal therapy. The latter developed a locoregional relapse after 4 years and was treated with mastectomy and chemotherapy. One patient (case 4) had a distant metastasis after 2 years of follow-up and received chemotherapy. The three other patients were free of relapse during their follow-up period. CONCLUSION: Primary axillary breast carcinoma is a rare entity. Despite the paucity of literature, our findings and authors' recommendations suggest that local excision can be performed safely with promising outcomes in this subset of patients.

Second-generation hormonotherapy in prostate cancer and bone microenvironment.

Prostate cancer (Pca) is the most commonly diagnosed cancer affecting men in France. Before the age of 75 years old, 1 in 8 French men will have Pca. Androgen deprivation therapies (ADT) remain the standard of care. Such therapies induce significant bone loss. The bone-remodelling cycle depends on the androgen synthesis signalling pathways. Furthermore, age-specific hormonal decline plays a key role in the decrease in bone mass. As a result, the older the patients, the more likely they are to have osteoporosis if they are treated with hormone therapy. Their risk of osteoporotic fracture has an impact on their quality of life and their capacity of independent living. In recent years, newer hormone therapies (acetate abiraterone, enzalutamide, apalutamide and darolutamide) have proved efficient in metastatic castration-resistant Pca (mCRPC) patients as well as in hormone naïve patients, and actually in nonmetastatic diagnosis. The combination of these treatments with ADT highly inhibit androgen production pathways. They are prescribed to aged patients undergoing bone density loss after first-generation antiandrogen treatment. Specific recommendations for bone health management in Pca patients are currently lacking. To date, bone mineral density in patients treated with second-generation hormone therapy has never been assessed in a prospective study. This review aims at reviewing what is known about the impact of second-generation hormonotherapy on bone microenvironment.

Alpelisib for the treatment of PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer.

Introduction: Two-thirds of advanced breast cancers are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-). Gene mutations in PIK3CA, encoding the PI3K catalytic subunit alpha of phosphatidyl-inositol 3-kinase (PI3K), are a frequent event in this population and are implicated in hormone therapy resistance. Alpelisib is a PI3K-alpha inhibitor and is the first PI3K inhibitor approved, in association with fulvestrant, by the FDA and EMA, based on improved progression-free survival (PFS) versus fulvestrant alone in a randomized phase III trial in HR+/HER2-, PIK3CA-mutated tumors following progression on/after HT.Areas covered: The scientific rationale, preclinical development, pharmacokinetics, and clinical efficacy/safety of alpelisib-fulvestrant are summarized. The role of alpelisib in the clinical setting is discussed, referencing current therapeutic options and clinical challenges associated with alpelisib's safety profile.Expert opinion: Alpelisib is an option for patients with HR+/HER2-, PIK3CA-mutated tumors whose disease progressed during/after aromatase inhibitor treatment. The PFS benefit appears clinically significant over fulvestrant alone, with a 7.9 months, non-significant, improvement in overall survival. Its safety profile requires strict patient selection, mainly based on baseline glycemic status, and close monitoring.

A review of new hormonal therapies for prostate cancer in black men: is there enough data?

BACKGROUND: Prostate cancer among black men is known to have specific molecular characteristics, especially the androgen receptor or enzymes related to the androgen metabolism. These targets are keys to the action of new hormonal therapies. Nevertheless, literature has a lack of data regarding black men. We aimed to gather the available literature data on new hormonal therapies among black populations. METHODS: We conducted a literature review from the PubMed / MEDLINE database until October 2020. All clinical studies of new hormonal therapies and black populations, regardless of methodology, were included. RESULTS: Four studies provided data on new hormonal therapies in black populations. Three studies reported a PSA decline in black patients treated with Abiraterone, higher in black men than in white men. Overall survival also appears to be higher in black patients treated with Abiraterone only or first. CONCLUSION: Few articles have evaluated the effectiveness and safety of use of these treatments among black populations. The first results seem to show that Abiraterone can provide a benefit in overall survival in black populations. Prospective studies are needed to answer these questions in the future.

Solitary prostate cancer liver metastasis: an exceptional indication for liver resection.

INTRODUCTION: Prostatic cancer metastases (PCM) are usually systemic. Isolated PCM liver metastases (PCLM) are very rare. The treatment of PCM consists of hormono- and chemotherapy eventually combined with stereotactic radiation. PATIENT AND DISCUSSION: A case of a 67-year old man presenting with a solitary, metachronous PCLM undergoing a left extended hepatectomy due to resistance to hormono- and chemotherapy is reported. He died of recurrent systemic disease 31 months later. CONCLUSIONS: The very rare indication and possible role of liver resection in the treatment of PCLM is discussed.

Uveal Effusion Syndrome as the Initial Manifestation of Primary Sjögren's Syndrome and Review of the Literature.

Purpose: The authors report a38-year-old woman with primary Sjögren's syndrome who initially showed recurrent blurred vision caused by uveal effusion syndrome and later developed dry mouth, dry eyes, and arthralgia. During the 5-year-course of disease, the patient's 3-time-onset was all manifested as blurred vision after decreased immunity. Despite the initial absence of sufficient immunological evidence, the final presence of positive serum anti-SS-A, rheumatoid factors, ANA, and inflammatory findings in minor salivary gland biopsy indicated primary Sjögren's syndrome.Methods: Retrospective review of a case note.Conclusions: The manifestation of UES requires further exploration of its real pathogenesis, and the possibility of systemic disease should never be excluded.

Endometrial Cancer: When Upfront Surgery Is Not an Option.

Background and Summary: The management of endometrial cancer, in an ever-older population with considerable comorbidity, remains a challenge for gynecological and radiation oncologists. Key Message: The present paper reviews literature data on treatment options for endometrial cancer patients unfit for surgery.

Rare ovarian tumours. Other treatments for ovarian cancer.

AIM: The description of rare malignant ovarian tumours and the most suitable treatments. Alternative therapies different from intravenous chemotherapy are also explained. METHODS: Literature review and ongoing trial information have been used to elaborate this guide. RESULTS: Each ovarian cancer type must be identified and treated properly from diagnostic to surgery, adjuvant treatment and metastatic disease. Hormonotherapy can be useful as an alternative treatment, especially in low-grade ovarian cancer and endometrioid subtype. Tumour characterisation is appropriated for treatment selection when targeted therapy is indicated. MEK inhibitors, tyrosine-kinase inhibitors, EGFR inhibitors, therapies against integrins, antibody-drug conjugates and other strategies are described. Antiangiogenics, PARP inhibitors and immunotherapy are discussed in other parts of this publication. CONCLUSION: Different ovarian cancer types must receive the appropriated treatment. Alternative therapies may be evaluated beyond the standard therapy, frequently in a clinical trial, and an individualised molecular study may help to find the best treatment.