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The cell proliferation-associated antigen Ki 67 and the immunohistochemical content of oestrogen receptors (ER), progesterone receptors AB (PRAB) and progesterone receptors B (PRB) were evaluated in leiomyomata and adjacent myometrium during the menstrual cycle and in leiomyomata under gonadotrophin-releasing hormone agonist (GnRHa) therapy. The proliferative status of muscular cells was measured by evaluating the percentage of nuclei staining positive for Ki 67 (proliferation index). Quantitative analysis (QH-score) was carried out using advanced stereographic computer technology to investigate ER, PRAB and PRB. Leiomyoma and myometrial biopsies were taken from 30 patients undergoing hysterectomy or myomectomy because of symptomatic leiomyomata (subgroup I). Leiomyoma biopsies were taken from 10 patients suffering from symptomatic submucosal leiomyomata, after 2 month GnRH therapy (subgroup II). During the secretory phase, the proliferation index (Ki 67) was found to be higher in leiomyomata than in myometrium, but the difference was not significant. Oestrogen receptor content was significantly higher in leiomyomata than in myometrium only during the proliferative phase of the cycle. PRAB and PRB content were found to be higher in leiomyomata than in adjacent myometrium with a statistically significant dominance of PRAB over PRB. Under GnRHa therapy, a dramatic decrease was observed in PRAB and B content as well as Ki 67 but ER content remained comparable with the results obtained during the menstrual cycle. The results suggest that leiomyomata may be under the influence of progesterone which may play a major role in their growth. [ABSTRACT FROM AUTHOR]

Background: To determine the incidence of reversible amenorrhea in women with breast cancer undergoing adjuvant anthracycline-based chemotherapy with or without docetaxel.Methods: We studied the incidence and duration of amenorrhea induced by two chemotherapy regimens: (i) 6 cycles of 5-fluorouracil 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 every 3 weeks (6FEC) and (ii) 3 cycles of FEC 100 followed by 3 cycles of docetaxel 100 mg/m2 on day 1 every 3 weeks (3FEC/3D). Reversible amenorrhea was defined as recovery of regular menses and, where available (101 patients), premenopausal hormone values (luteinizing hormone (LH), follicle-stimulating hormone (FSH) and estradiol) in the year following the end of chemotherapy.Results: One hundred and fifty-four premenopausal patients were included: 84 treated with 6FEC and 70 with 3FEC/3D. The median age was 43.5 years (range: 28-58) in the 6FEC arm and 44 years (range: 29-53) in the 3FEC/3D arm. Seventy-eight percent of patients were treated in the context of the PACS 01 trial. The incidence of chemotherapy-induced amenorrhea at the end of chemotherapy was similar in the two groups: 93 % in the 6FEC arm and 92.8 % in the 3FEC/3D arm. However, in the year following the end of chemotherapy, more patients recovered menses in the 3FEC/3D arm than in the 6FEC arm: 35.5 % versus 23.7 % (p = 0.019). Among the 101 patients for whom hormone values were available, 43 % in the 3FEC/3D arm and 29 % in the 6FEC arm showed premenopausal levels one year after the end of chemotherapy (p < 0.01). In the 3FEC/3D group, there was a statistically significant advantage in disease-free survival (DFS) for patients who were still amenorrheic after one year, compared to patients who had recovered regular menses (p = 0.0017).Conclusion: Our study suggests that 3FEC/3D treatment induces more reversible amenorrhea than 6FEC. The clinical relevance of these findings needs to be investigated further. [ABSTRACT FROM AUTHOR]

Transgender women experience gender dysphoria due to a gender assignment at birth that is incongruent with their gender identity. Transgender people undergo different surgical procedures and receive sex steroids hormones to reduce psychological distress and to induce and maintain desired physical changes. These persons on feminizing hormones represent a unique population to study the hormonal effects on breast development, to evaluate the risk of breast cancer and perhaps to better understand the precise role played by different hormonal components. In MTF (male to female) patients, hormonal treatment usually consists of antiandrogens and estrogens. Exogenous hormones induce breast development with the formation of ducts and lobules and an increase in the deposition of fat. A search of the existing literature dedicated to hormone regimens for MTF patients, their impact on breast tissue (incidence and type of breast lesions) and breast cancer risk provided the available information for this review. The evaluation of breast cancer risk is currently complicated by the heterogeneity of administered treatments and a lack of long-term follow-up in the great majority of studies. Large studies with longer follow-up are required to better evaluate the breast cancer risk and to understand the precise mechanisms on breast development of each exogenous hormone.

Background: Reducing side effects of cancer treatments is a major challenge for clinicians involved in the management of breast cancer patients., Methods: We analyzed data from 63 patients (32 in the general anesthesia group and 31 in the hypnosis sedation group) who were included in 1 prospective non-randomized trial evaluating hypnosis sedation in breast cancer treatment. The patients were followed every 3 months for 2 years. All patients received neoadjuvant chemotherapy with 4 cycles of epirubicin and cyclophosphamide followed by taxanes. Thereafter, patients underwent surgery while on general anesthesia or while on hypnosis sedation. Radiotherapy was administered according to institutional guidelines. Endocrine therapy was prescribed if tumors expressed hormone receptors. Prevalence, intensity and duration of polyneuropathy, musculoskeletal pain, postoperative pain and cancer-related fatigue were assessed at each medical visit., Results: Symptoms duration was statistically reduced for polyneuropathy ( p < 0.05), musculoskeletal pain ( p < 0.05) postoperative pain and cancer-related fatigue ( p < 0.05) in the hypnosis group., Conclusion: Despite the limitations of this study (lack of randomization and small size) we conclude that hypnosis sedation may exert a role on different side effects of breast cancer treatment in patients receiving neoadjuvant chemotherapy, mainly by reducing their duration.

Background: Pain after breast cancer surgery remains largely unexplained and inconsistently quantified. This study aims to describe the perioperative pain patterns in patients with breast cancer, up to two years after surgery., Methods: This is a pre-planned sub-study of the Ketorolac in Breast Cancer (KBC) trial. The KBC trial was a multicentre, prospective, double-blind, placebo-controlled, randomised trial of a single dose of 30 mg of ketorolac just before breast cancer surgery, aiming to test its effect on recurrences. This sub-study focuses only on pain outcomes. From 2013 to 2015, 203 patients were randomised to ketorolac ( n = 96) or placebo ( n = 107). Structured questionnaires were delivered by telephone after one and two years, exploring the presence, location, permanence, and frequency of pain. Patients' perceptions of pain were captured by an open-ended question, the responses to which were coded and classified using hierarchical clustering., Results: There was no difference in pain between the ketorolac and the placebo group. The reported incidence of permanent pain was 67% and 45% at one and two years, respectively. The largest category was musculoskeletal pain. Permanent pain was mainly described in patients with musculoskeletal pain. The description of pain changed in most patients during the second postoperative year, i.e., moved from one category to another (no pain, permanent, or non-permanent pain, but also, the localisation). This phenomenon includes patients without pain at one year., Conclusions: Pain is a complex phenomenon, but also a fragile and unstable endpoint. Pain after breast cancer surgery does not necessarily mean breast pain but also musculoskeletal and other pains. The permanence of pain and the pain phenotype can change over time.

Background: Ketorolac has been associated with a lower risk of recurrence in retrospective studies, especially in patients with positive inflammatory markers. It is still unknown whether a single dose of pre-incisional ketorolac can prolong recurrence-free survival., Methods: The KBC trial is a multicenter, placebo-controlled, randomized phase III trial in high-risk breast cancer patients powered for 33% reduction in recurrence rate (from 60 to 40%). Patients received one dose of ketorolac tromethamine or a placebo before surgery. Eligible patients were breast cancer patients, planned for curative surgery, and with a Neutrophil-to-Lymphocyte Ratio≥4, node-positive disease or a triple-negative phenotype. The primary endpoint was Disease-Free Survival (DFS) at two years. Secondary endpoints included safety, pain assessment and overall survival., Findings: Between February 2013 and July 2015, 203 patients were assigned to ketorolac (n = 96) or placebo (n = 107). Baseline characteristics were similar between arms. Patients had a mean age of 55.7 (SD14) years. At two years, 83.1% of the patients were alive and disease free in the ketorolac vs. 89.7% in the placebo arm (HR: 1.23; 95%CI: 0.65-2.31) and, respectively, 96.8% vs. 98.1% were alive (HR: 1.09; 95%CI: 0.34-3.51)., Conclusions: A single administration of 30 mg of ketorolac tromethamine before surgery does not increase disease-free survival in high risk breast cancer patients. Overall survival difference between ketorolac tromethamine group and placebo group was not statistically significant. The study was however underpowered because of lower recurrence rates than initially anticipated. No safety concerns were observed., Trial Registration: ClinicalTrials.gov NCT01806259., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The main aim of this prospective nonrandomized study was to evaluate if mastectomy performed with perioperative hypnosedation led to a lower incidence of chronic pain compared with mastectomy under general anesthesia. Methods: Forty-two breast cancer patients who underwent mastectomy either under GA (GA group, n = 21) or HYP (HYP group, n = 21) associated with local and/or regional anesthesia were included. The type of adjuvant therapy as well as the number of reconstructive surgical procedures were well balanced between the 2 groups. The average age of the patients and the type of axillary surgery were also equivalent. Incidence of postmastectomy chronic pain, lymphedema, and shoulder range of motion (ROM) were evaluated after a mean 4-year follow-up. Results: The study shows a statistically significant lower incidence of postmastectomy chronic pain in HYP group (1/21, 1 patient out of 21 experiencing pain) compared with GA group (9/21) with 9 patients out of 21 experiencing pain ( P = .008). ROM for shoulder was also less frequently affected in the hypnosedation group, as only 1 patient had decreased ROM, instead of 7 in the other group ( P = .04). Conclusions: Our study is the first to hint at the potential benefits of hypnosedation on postmastectomy chronic pain. Despite the limitations of this study (nonrandomized, small sample), preliminary results merit further study of hypnosedation.

Introduction: Inflammatory biomarkers and scores are important prognostic factors in breast cancer, and are proposed during the perioperative period. Here, we investigate their correlation and concordance in breast cancer surgical patients., Patients and Methods: With the IRB approval and written informed consent, we included 14 patients (median age: 61 [41 to 82] years) scheduled for conservative surgery (n = 12) or mastectomy (n = 2) for breast cancer. We measured, at baseline, day+1 and day+8, albumin (Alb), C-Reactive Protein (CRP), total white blood cell counts (WBC), lymphocytes (L) and neutrophils (N) counts, and calculated the following inflammatory scores: Neutrophil-to-lymphocyte ratio (NLR), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI) and Prognostic Nutritional Index (PNI). A linear regression model is used to compare CRP and NLR, and the Kappa statistic to detect discordance (<0) or agreement (>0.4) between the scores., Results: We measured 170 laboratory values and calculated 182 inflammatory scores. CRP, WBC, N and NLR are significantly different at day+1 compared with baseline (respectively, at baseline, day+1 and day+8 (median[IQR 25-75]): CRP: 0.1[0.1-0.6], 0.85[0.2-1.18], 0.18[0.1-0.4]mg/dL; WBC: 6.36[5.91-7.16], 7.45[6.38-8.16], 7.73[6.25-8.54] × 10(3)/mm(3); N: 3.78[3.21-4.2], 5.05[4.37-5.99] × 10(3)/mm(3); and NLR: 1.95[1.67-2.46], 2.62[2.36-3.73], 2.23[1.46-2.43]) (P < 0.05 for all the comparisons between baseline and day+1). Alb and L tend to decrease (P = 0.06). Discordance is clear between all the inflammatory scores (NLR, mGPS, PI, PNI) (Kappa<0)., Conclusion: Inflammatory biomarkers and scores, like CRP, WBCs, N, NLR, PNI, and PI are modified after a breast cancer surgery, but with discordance and no interchangeability., (Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Inflammation is associated with a worse outcome in cancer and neutrophil:lymphocyte ratio (NLR) is a strong prognostic value. In cancer, nonsteroidal anti-inflammatory drugs (NSAIDs) could be of interest. We investigated the prognostic significance of NLR and the impact of intraoperative NSAIDs in cancer surgeries., Methods: We performed an observational study in early breast, kidney, and lung cancers (357, 227, and 255 patients) with uni- and multivariate analyses (Cox model)., Results: In breast cancer (Centre 1), NLR ≥ 4 is associated with a higher risk of relapse (hazards ratio (HR) = 2.41; 95 % confidence interval (CI) 1.01-5.76; P = 0.048). In breast cancer (Centre 2), NLR ≥ 3 is associated with a higher risk of relapse (HR = 4.6; 95 % CI 1.09-19.1; P = 0.04) and higher mortality (HR = 4.0; 95 % CI 1.12-14.3; P = 0.03). In kidney cancer, NLR ≥ 5 is associated with a higher risk of relapse (HR = 1.63; 95 % CI 1.00-2.66; P = 0.05) and higher mortality (HR = 1.67; 95 % CI 1.0-2.81; P = 0.05). In lung cancer, NLR ≥ 5 is associated with higher mortality (HR = 1.45; 95 % CI 1.02-2.06; P = 0.04). The intraoperative use of NSAIDs in breast cancer patients (Centre 1) is associated with a reduced recurrence rate (HR = 0.17; 95 % CI 0.04-0.43; P = 0.0002) and a lower mortality (HR = 0.25; 95 % CI 1.08-0.75; P = 0.01). NSAIDs use at the beginning of the surgery is independently associated with a lower metastases risk after lung cancer surgery (HR = 0.16; 95 % CI 0.04-0.63; P = 0.009). Ketorolac use is independently associated with longer survival (HR = 0.55; 95 % CI 0.31-0.95; P = 0.03)., Conclusions: In these cohorts, these analyses show that NLR is a strong perioperative prognosis factor for breast, lung, and kidney cancers. In this context, intraoperative NSAIDs administration could be associated with a better outcome.

Background: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy., Materials and Methods: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I) and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II). All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol). Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year). All data were retrospectively evaluated in 2011., Results: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year) b: Oligomenorrhea (5 to 9 cycles/year) c: Severe oligomenorrhea (1 to 4 cycles/year) d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values., Conclusions: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status. These data are very important for the choice of endocrine therapy.

Background: Whether intraoperative analgesics have an impact on postoperative cancer recurrence is unknown. Some investigations suggest that the opioids could favor relapse and that regional analgesia and nonsteroidal antiinflammatory drugs could improve cancer prognosis. We retrospectively reviewed our series of breast cancer surgery patients., Methods: This retrospective study included 327 consecutive women who underwent mastectomy with axillary dissection for breast cancer. The main objective was to compare the incidence of cancer recurrence among patients who received different analgesics during surgery., Results: Perioperative characteristics, cancer prognostic factors, and the length of surgery were comparable regardless of the analgesics administered. Univariate and multivariate analyses showed a lower cancer recurrence rate when ketorolac was given before surgery (P = 0.019). Other analgesics (sufentanil, ketamine, and clonidine) were not associated with a significant reduction in cancer recurrence rates in our series., Conclusion: This retrospective analysis suggests that intraoperative administration of ketorolac decreases the risk of breast cancer relapse compared with other analgesícs.

Objective: To assess the safety of fertility-sparing treatment and the remaining chance of childbearing after surgery., Design: Retrospective clinical study., Design: Gynecology department of a university teaching hospital., Patient(s): Seventy-five women underwent surgical management in our institution between 1986 and 2001 for borderline tumors of the ovary., Intervention(s): Fifty-nine patients were treated by radical, fertility-compromising surgery. The remaining 16 patients underwent conservative surgery, preserving the uterus and at least some functional ovarian tissue. Seven unilateral adnexectomies, one simple cystectomy, and two adnexectomies associated with contralateral cystectomy were performed., Main Outcome Measure(s): Recurrence, survival, and pregnancy rates., Result(s): The observed recurrence rates after radical and conservative surgery were 0.0% and 18.7%, respectively. No disease-related deaths occurred in any group; there is no significant difference in survival rates. We can report 12 pregnancies in 7 of 11 women who underwent fertility-sparing management and who wished to become pregnant., Conclusion(s): In certain circumstances, conservative management offers a safe solution for borderline tumors of the ovary. Recurrence is noted significantly more often after this type of treatment, but all cases of recurrent disease can be detected with close follow-up and can be treated accordingly. No significant change in survival rates was found. Moreover, the pregnancy rate in women desiring pregnancy, those treated conservatively, was as high as 63.6%.