Survival outcome and treatment tolerability for postmenopausal females with early stage hormone receptor positive breast cancer treated with different adjuvant hormonal lines (TAM vs. AI vs. switching strategy) for 5 years

Background The standard adjuvant endocrine treatment for postmenopausal female patients with hormone receptor positive early breast cancer was 5 years of tamoxifen, but recurrence and side effects restrict its usefulness. The aromatase inhibitor (anastrozole or exemestane or letrozole) was compared with tamoxifen for 5 years or started after completing 2-3 years of tamoxifen in postmenopausal female patients diagnosed with early breast cancer at "Ain Shams University Hospitals" Objective The aim of the study was to measure survival outcome and treatment tolerability for postmenopausal females with Hormone Receptor Positive early breast cancer who received adjuvant hormonal treatment with tamoxifen [TAM] only for 5 years versus those who received adjuvant hormonal treatment with tamoxifen [TAM] for 2 years switching to aromatase inhibitors [AI] in the sequential 3 years versus those who received adjuvant hormonal treatment with aromatase inhibitors [AI] solely for 5 years. Patients and methods This study included 100 postmenopausal women with early breast cancer who presented at the Clinical Oncology Department, Ain Shams University, in the interval from January 2010 until December 2015. Conclusion Similar disease free survival and overall survival were observed among the three studied groups. Switching tamoxifen to aromatase inhibitors provides better tolerability in terms of endometrial thickness when compared to 5 years of tamoxifen monotherapy. Patients who administer aromatase inhibitor included in the switching strategy experience less osteoporosis and less generalized bone pain compared to upfront aromatase inhibitor to 5 years. There was a significant improvement of disease free survival (DFS) in human epidermal growth factor receptor 2 (HER 2) negative patients receiving any adjuvant hormonal treatment line for five years in comparison to HER 2 positive patients receiving the same adjuvant hormonal treatment for five years.

Primary Subcutaneous Umbilical Endometriosis: Case Report and Review of the Literature

We report the case of a patient diagnosed with primary umbilical endometriosis intending to discuss the diagnostic and therapeutic management of this rare disease. A 45-year-old woman suffering from a painful swelling located in the umbilical region, with intact and normal cutaneous aspect, came to our attention. Ultrasonography of the umbilical region showed a nodule with a nonhomogeneous echotexture pattern. Partial omphalectomy was performed under local anesthesia in day care setting surgery. Histology confirmed the diagnosis of umbilical endometriosis. Pre- and postoperative clinical controls showed no evidence for other endometriosis localization. No medical treatment was administered. No signs of recurrence were observed after 5 years from surgery. A review of the literature of the last 10 years was generated based on MEDLINE research, selecting some specific keywords. Several lesions can occur in the umbilical region, and endometriosis has to be ruled out even in patients without any surgery in their medical history. Surgery is the gold standard treatment for this condition: partial and radical omphalectomy are the two treatment options. We believe that given the significant psychological and aesthetical value of the umbilicus, surgical treatment has to be tailored and in case of a small endometrial umbilical nodule, partial omphalectomy (local excision of the umbilical endometrial nodule) with a 3 mm free border, even without adjuvant hormonal treatment, could ensure adequate and effective treatment.

Using miR-125b in the Prediction of Aromatase Inhibitors Resistance in Metastatic Breast Cancer

Background: Several studies investigated the miRNAs in cancer trying to assess the prognosis or to predict the response to certain treatment .One of these miRNAs are miR 125b , it was suggested by previous results as a good marker for prediction of aromatase inhibitors (AI) response. So, this study was conducted to assess the value using miRNA125b as a predictive factor to AI response. Patients and Methods: A total of 90 patients of postmenopausal HR+ve metastatic breast cancer who attended to medical oncology department outpatient’s clinic in SECI, Assiut university Egypt, from May 2017 to September 2018. Patients presented with metastasis at diagnosis as well as patients who relapsed only after 3 years of adjuvant hormonal treatment with SERM were included. All patients received AI as first line treatment for metastatic, miRNA 125b was isolated from peripheral blood samples and measured by using (q PCR).The response of patients was assessed by RECIST criteria and correlated with its expression levels. Results: Expression of the miR125-b was significantly higher in patients than control p= 0.000. However, no significant difference in its expression between those with single of multiple metastases or even between the site of metastases. We didn’t find also any significant difference in response p=0.648 and survival either PFS p=0.406 or OS p=0.384 between those patients with high expression vs. low expression. Conclusion: Our results suggest that miR125b could be used as a diagnostic marker as it is significantly increased in patients than control. However, we don’t recommend using miR125b as a marker to predict the AI resistance as further studies with large sample size are needed to confirm these results.

Administration of pharmaceutical agents prior to testicular sperm extraction procedures: A meaningful or meaningless approach?

Background: To date, no randomized and controlled study has demonstrated effect of adjuvant medical therapy on testicular sperm production before the sperm retrieval procedures in men with non-obstructive azoospermia (NOA). Objectives: To present the available data on administration of pharmaceutical agents prior to testicular sperm extraction (TESE) procedures in order to obtain better sperm retrieval results in men with NOA. Methods and Results: Various pharmaceutical agents used empirically to induce spermatogenesis in the treatment of NOA. The rationale for adjuvant hormonal treatment has been to increase intratesticular testosterone levels with different dosages of gonadotropins, anti-estrogen agents or aromatase inhibitors. Conclusion: Based on the published studies, in the presence of normal range of peripheral serum total testosterone level, no medical treatment is advised, and TESE procedures should be performed directly in men with NOA. Further well-designed and randomized, placebo controlled trials are needed to support the potential benefit of pretreatment prior to TESE procedures.

Effects of ‎tamoxifen on the reproductive system of female breast cancer patients: an ultrasound-based cohort study

Background: Tamoxifen (TMX) is regarded as standard treatment for breast cancer (BC) patients‎. In recent years, several studies have reported gynecological side effects and due to TMX's estrogenic effects. Here, we evaluate the side effects of TMX on the ‎endometrium and ovaries of female BC patients. Methods: This was an ultrasound-based cohort study conducted in three oncology centers in Baghdad, Iraq. A total of ‎‎255 female patients were included, 140 premenopausal (PreM) and 115 postmenopausal (PostM), with estrogen receptor (ER)-positive BC using TMX adjuvant hormonal treatment for at least three months after surgery and adjuvant ‎chemo/radiotherapy.‎ Ultrasound (US) on the endometrium and ovaries of the women following ‎BC surgery/chemotherapy (baseline) and at 3, 6, 12, and 24 months following was performed‎. Data collected included age, menopausal status, co-morbid chronic illness and medications, including duration of TMX treatment. Results: Presence of ovarian cyst was significantly higher in the PreM ‎compared to PostM ‎women, while there were no significant differences for other gynecological findings.‎ At ‎baseline, endometrial thickness (ET) was significantly higher in the PreM compared to the PostM women. In both groups, women with increased ET became more frequent from baseline to 3 ‎months, from 3 to 6 ‎months, from 6 to 12 months, and from 12 ‎ to 24 months. At all time periods, ‎women with increased ET was ‎significantly higher in the PostM compared PreM women, resulting ‎in a risk of ET increase by 6 folds (ranging from 3 – ‎‎11 folds) ‎in PostM compared to PreM women. Conclusions: Longer duration of TMX is associated with increased ET. Duration of TMX did not appear to increase the risk of various gynecological outcomes, for example endometrial cancer rate was low. Finally, there was an increase in ET, which appeared to be six-folds higher in PostM compared to PreM women.‎

Gynecologic Cancer InterGroup (GCIG) Consensus Review for Endometrial Stromal Sarcoma

Endometrial stromal sarcoma (ESS) accounts for approximately 20% of all uterine sarcomas and presents, at a mean age, around 50 years of age. Half of the patients are premenopausal. ESS often manifests as an endometrial polyp and 60% of cases present with FIGO stage I disease. The natural history is one of slow growing indolent disease. Typical microscopic findings include a uniform population of endometrial stromal-type cells invading the myometrium and myometrial vessels. Imaging studies cannot reliably diagnose ESS preoperatively, so surgical resection for a presumed fibroid is a common scenario. Hysterectomy is the cornerstone of treatment for localized ESS, but morcellation should be avoided. Systematic lymphadenectomy in ESS does not improve the outcome. Leaving the ovaries in situ does not worsen survival and this is of importance especially for young women. The data support the current practice to administer adjuvant hormonal treatment, although several questions remain, such as optimal doses, regimens (progestins or aromatase inhibitors) and duration of therapy. Repeat surgery for recurrent disease that is indolent and hormone sensitive appears to be an acceptable approach. Systemic treatment for recurrent disease is mainly hormonal.

Use of mutational profiling of metastatic ER+/HER2- breast cancers and the coexistence of KRAS, MET, BRAF, and FGFR3 with PIK3CA mutations.

11003 Background: ER+/HER2- breast cancers (BCs) constitute the most frequent BC subtype. Their response to endocrine therapy and degree of estrogen dependence are heterogeneous. There is little data available about the genetic changes associated with disease progression in this subtype. This information could facilitate drug development. Methods: A series of 132 ER+/HER2- BC patients diagnosed between 1982 and 2008, with known local-regional (n=10) or distant (n=98) relapse or both (n=24), and available FFPE blocks from their primary (P; n=132) and paired relapse (R; n=49) were identified at a single institution. ER and HER2 status were centrally confirmed. 120 mutations from 11 actionable genes and PTEN protein expression were determined using Fluidigm-based real-time PCR and IHC, respectively. Results: At primary diagnosis, median age was 57 years (27-90); median tumor size 2.5 cm (0.5-11); 75% had positive nodes, 26.5% were pre-menopausal; 80% received adjuvant hormonal treatment. Mutation frequency in P and R samples is presented in the Table. PIK3CA mutations were identified in 44% (58/132) P samples. HRAS, AKT1 and PIK3CA mutations were mutually exclusive. 62.5% (5/8) of KRAS-mutated, 75% (6/8) of MET-mutated, 100% (2/2) of BRAF-mutated and 33.3% (1/3) of FGFR3-mutated P had coexistent PIK3CA mutations. For the 49 evaluated pairs, high concordance for the mutations status was found between P and R. Conclusions: KRAS, BRAF, MET and FGFR3 mutations, found at relatively high frequency in this population of relapsed ER+/HER2- BCs, could represent clinically relevant targets and contribute to mechanisms of recurrence, particularly in PIK3CA-mutated BCs. Mutation profiling of additional paired samples is ongoing and clinical outcome data will be presented. [Table: see text]