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Endometriosis is a benign gynecological condition which induces a chronic inflammatory process, characterized by the presence of endometrium-like tissue outside the uterus. Treatment options for endometriosis include medical, surgical, or both. Irrespective of the treatment approach, recurrence of symptoms is not rare. We report the use of radiotherapy in a patient with recurrent refractory endometriosis, not responding to conventional treatments. At lower doses, radiotherapy can modulate the inflammatory cascade and can also does ovarian ablation. She was treated using 6MV photons with a four-field box to a total dose of 30Gy in 10 fractions. The pelvic radiotherapy field also included the ovarian remnant. Her symptoms regressed within one week of radiation treatment and is now symptom free for six months, with good quality of life. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant ovarian function suppression (OFS) in premenopausal hormone receptor (HR) positive breast cancer (BC) improves survival. Adherence to adjuvant gonadotropin-releasing hormone analogs (GnRHa) remains a challenge and is associated with toxicities and inconvenient parenteral administration. The goal of this study was to describe real-world adherence patterns and patient preferences surrounding adjuvant GnRHa. Methods: We analyzed the medical records of premenopausal women with non-metastatic HR positive BC from January 2000 to December 2017; participants received adjuvant monthly goserelin or leuprolide at The Ohio State University. Data collected included demographics, clinicopathologic characteristics, and OFS adherence/side effects. We defined non-adherence as discontinuation of GnRHa within 3 years for a reason other than switching to an alternate OFS, delay > 7 days from a dose, or a missed dose. Chi-square tests assessed associations between clinical characteristics and outcomes. Results: A total of 325 patients met eligibility. Of these, 119 (37%) patients were non-adherent to GnRHa; 137 (42%) underwent elective bilateral salpingo-oophorectomy after initial GnRHa. Those opting for surgery reported significantly more hot flashes (74% vs 48%, p < 0.001), arthralgias (46% vs 30%, p = 0.003), and vaginal dryness (37% vs 21%, p = 0.001) compared with patients remaining on GnRHa. Conclusion: Non-adherence to adjuvant GnRHa occurred in over a third of patients and almost half the patients initiating GnRHa underwent subsequent surgical ablation. These high frequencies highlight real-world patterns of OFS. Additionally, treatment toxicities may impact personal preference of OFS modality. Personalized practices to target predictors of adjuvant GnRHa non-adherence are critical to optimize symptoms, adherence, and survivorship. [ABSTRACT FROM AUTHOR]

Ovarian suppression (OS) is an effective therapy in hormone-sensitive breast cancer. Oophorectomy and ovarian irradiation have historically been used to achieve the goal of ovarian ablation. Luteinizing hormone releasing hormone (LHRH) analogues have largely supplanted surgical and radiation-based approaches because of less side effects and a lower likelihood of permanent amenorrhea, with the potential for restoration of fertility. LHRH analogues goserelin, buserelin, leuprorelin are equally effective. Buserelin is economically attractive.

The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin (‘Zoladex’) and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer.

Background The effect of ovarian ablation or suppression (OAS) in premenopausal women with breast cancer is controversial. The overall survival (OS), disease-free survival (DFS) and adverse event of OAS versus no OAS were compared. Methods A literature review of EMBASE, Web of Science, PUBMED, and Cochrane Library was conducted. The hazard ratio (HR) and 95% confidence interval (CI) for OS and DFS, as well as risk ratio (RR) and 95% CI for adverse events were evaluated. I-squared statistic ( I 2 ) represents heterogeneity. Results Twenty-nine studies with a total of 21,249 women were included. In premenopausal women aged 40 years or younger, there were significant differences in OS (HR 0.78, 95% CI: 0.66–0.94, P = 0.008, I 2 = 0%) and DFS (HR 0.84, 95% CI: 0.73–0.97, P = 0.02, I 2 = 0%) between OAS and no OAS. In advanced stage breast cancer, a significant difference was found in OS (HR 0.76, 95% CI: 0.60–0.96, P = 0.02, I 2 = 0%). Patients treated with OAS had more chances to have hot flushes (RR 1.91, 95% CI: 1.62–2.26, P < 0.01, I 2 = 0%) and vaginal dryness (RR 1.19, 95% CI: 1.08–1.31, P = 0.0003, I 2 = 0%). No significant difference in depression (RR 1.28, 95% CI: 0.94–1.74, P = 0.12, I 2 = 0%). Conclusions The study shows that OAS plays a beneficial role in premenopausal women aged 40 years or younger and advanced stage breast cancer. However, OAS is associated with increase in hot flushes and vaginal dryness. [ABSTRACT FROM AUTHOR]

Historically, ovarian ablation (OA) was used as therapy for women with recurrent hormone-receptor-positive (HRP) premenopausal breast cancer. With the publication of the SOFT (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial) randomized trials, there is considerable interest in OA as an adjuvant treatment, either in combination with tamoxifen or an aromatase inhibitor (AI). Thus, we have reviewed current guidelines and key studies on this important topic and have highlighted the relevant biological and pharmacological aspects of the various endocrine therapies. The results of two key randomized trials addressing the use and controversies of OA in premenopausal breast cancer are discussed and recent research emphasizing the detrimental consequences of premature menopause and the cost-effectiveness of OA is presented. In low-risk patients with HRP premenopausal breast cancer, OA is not beneficial and tamoxifen remains the anti-hormone treatment of choice. In high-risk women (previous chemotherapy or women younger than 35), OA in combination with AI is more effective but is arguably not cost-effective, particularly when OA is achieved medically using a GnRH agonist/antagonist. Compared to tamoxifen alone, the SOFT trial showed a 4.5-7.7% reduction in breast cancer relapse using OA (in combination with either tamoxifen or AI) in high-risk women, though the 5-year overall survival benefit was limited (1.4-3.6%). Premature menopause is associated with long-term mortality risks and women often experience significant menopausal symptoms that impact on quality of life. These considerations should play a role in the treatment selection of those patients who may benefit from adjuvant OA. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common form of cancer that affects females, during lifetime, 1 of 8, 1 in 12 <1: 8/1: 12> (1) develops this type of cancer. Breast cancer incidence is steadily rising; genetic studies show that over the last 80 years there has been a three-fold increase in incidence both in the general population and at high-risk population (those showing BRCA 1, BRCA2 gene mutations). The incidence of breast cancer newly diagnosed in women of all ages in Romania in 2018 according to Globocan is 21.5% (9269 new cases diagnosed).(3) The Gail and Claus models are the most commonly used prediction models regarding breast cancer risk due to the high predictive value in assessing estrogen-receptor-positive (ER+). Therefore, it is necessary not only to establish a degree of prediction of the disease through these assessment models, but also to apply hygienicdietary measures, namely the initiation of prophylactic therapy, in order to prevent the disease. The interpretation of the Gail model, if the patient has a risk ≥ = 1.66%, is eligible for chemoprevention therapy with hormonal agents over the next 5 years. [ABSTRACT FROM AUTHOR]

The TEXT and SOFT trials concluded that an aromatase inhibitor (AI) with ovarian ablation (OA) yields a higher 5-year disease-free survival than tamoxifen alone in premenopausal ER+ high-risk early breast cancer. However, the long-term health consequences and costs of OA, either by GnRH agonist or oophorectomy, have not been evaluated. The objective was to conduct a cost-effectiveness analysis comparing tamoxifen to OA with AI. Markov Monte Carlo simulation model estimated the costs and benefits of 3 endocrine strategies: (1) tamoxifen; (2) GnRH agonist with AI (GnRHa-AI); (3) bilateral salpingo-oophorectomy with AI (BSO-AI). Effectiveness was measured in life expectancy gain (years), and costs were averaged over a lifetime (USD 2015). Adverse events and deaths from each strategy were modeled in the United States population over a time horizon of 40 years. For women without prior chemotherapy (low-risk), tamoxifen alone was more effective (18.03 years) and less costly ($1566) than GnRHa-AI (17.66 years, $93,692) or BSO-AI (17.63 years, $25,892). For those with prior chemotherapy (high-risk), BSO-AI was more costly but more effective (16.78 years, $25,368) than tamoxifen alone (16.55 years, $1523) with an ICER of $102,290, while GnRHa-AI yielded an ICER of $443,376. The simulation estimated 787 and 577 deaths attributable to OA among 9320 high-risk women after BSO-AI and GnRHa-AI, respectively. There may be a role for ovarian ablation in premenopausal women with ER+ high-risk early breast cancer; however, this analysis raises concerns about the long-term health consequences of ovarian ablation and the potential effects on overall survival. [ABSTRACT FROM AUTHOR]

Luteinising hormone releasing hormone agonists (LH-RHa) are effective in the treatment of advanced endocrine-sensitive breast cancer in premenopausal patients, but their role in the adjuvant setting has remained controversial for a long time. Tamoxifen for 5 years has been traditionally considered the standard endocrine therapy for premenopausal patients and this is still valid for many patients. However, the recently reported SOFT trial has suggested that adding ovarian function suppression (OFS) to tamoxifen could improve DFS in women at sufficient risk to warrant adjuvant chemotherapy and who remained premenopausal after this therapy. The administration of an aromatase inhibitor plus OFS represents an additional therapeutic option for hormone-receptor positive premenopausal breast cancer patients, according to the combined analysis of the SOFT and TEXT trials. Temporary ovarian suppression induced by LH-RHa has been recognized as an effective strategy to preserve ovarian function from the toxic effects of chemotherapy and is now recommended in young breast cancer patients with endocrine-insensitive tumors. In this review, we discuss recent data on the role of LH-RHa in combination with tamoxifen or with an aromatase inhibitor, and we comment on its role as a strategy to preserve ovarian function in young patients candidates for adjuvant or neo-adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

A 50-year-old woman was admitted to our hospital due to multiple lung nodules detected incidentally on a chest X-ray. A video-assisted thoracoscopic lung biopsy revealed low-grade endometrial stromal sarcoma (LG-ESS). She had undergone a simple hysterectomy 1 year earlier owing to a diagnosis of adenomyosis. A review of her previous hysterectomy specimen showed not endometriosis but LG-ESS. According to the patient's levels of serum follicle stimulating hormone and estradiol, she was in the premenopausal state with retained and normally functioning ovaries. She then underwent ovarian ablation by radiotherapy, after which she was administered 2.5 mg of letrozole once per day. Three months later, the size of the metastatic nodules in both lungs had decreased. The patient was followed up for 24 months while continuing on letrozole, and maintained a partial remission. We report herein on a case of metastatic LG-ESS treated with letrozole after ovarian ablation by radiotherapy. [ABSTRACT FROM AUTHOR]

Background Cancer Care Ontario's Program in Evidence-Based Care (PEBC) recently created an evidence-based consensus guideline on the systemic treatment of early breast cancer. The evidence for the guideline was compiled using a systematic review to answer the question "What is the optimal systemic therapy for patients with early-stage, operable breast cancer, when patient and disease factors are considered?" The question was addressed in three parts: cytotoxic chemotherapy, endocrine treatment, and HER2 (human epidermal growth factor receptor 2)—targeted therapy. Methods For the systematic review, the literature in the MEDLINE and EMBASE databases was searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major oncology guideline organizations were also searched. The basic search terms were "breast cancer" and "systemic therapy" (chemotherapy, endocrine therapy, targeted agents, ovarian suppression), and results were limited to randomized controlled trials (RCTS ), guidelines, systematic reviews, and meta-analyses. Results Several hundred documents that met the inclusion criteria were retrieved. Meta-analyses from the Early Breast Cancer Trialists' Collaborative Group encompassed many of the RCTS found. Several additional studies that met the inclusion criteria were retained, as were other guidelines and systematic reviews. Summary The results of the systematic review constitute a comprehensive compilation of high-level evidence, which was the basis for the 2014 PEBC guideline on systemic therapy for early breast cancer. The review of the evidence for systemic endocrine therapy (adjuvant tamoxifen, aromatase inhibitors, and ovarian ablation and suppression) is presented here; the evidence for chemotherapy and HER2-targeted treatment— and the final clinical practice recommendations—are presented separately in this supplement. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to assess the value of ovarian ablation using goserelin in premenopausal patients with stage II/III hormone receptor-positive breast cancer without chemotherapy-induced amenorrhea (CIA). Materials and Methods: We retrospectively reviewed the data of breast patients treated between October 1999 and November 2007 without CIA. The Kaplan-Meier method was used for calculation of the survival rate. Log rank method and Cox regression analysis were used for univariate and multivariate prognostic analysis. Results: The median follow-up period was 61 months. Initially, 353 patients remained without CIA after chemotherapy and 98 among those who received goserelin and tamoxifen (TAM). In univariate analysis, goserelin improved locoregional recurrence-free survival (LRFS) (98.9% vs. 94.1%, p=0.041), distant metastasis-free survival (DMFS) (85.4% vs. 71.9%, p=0.006), disease-free survival (DFS) (85.4% vs. 71.6%, p=0.005), and overall survival (OS) (93.5% vs. 83.5%, p=0.010). In multivariate analysis, goserelin treatment was an independent factor influencing DMFS (hazard ratio [HR], 1.603; 95% confidence interval [CI], 1.228 to 2.092; p=0.001), DFS (HR, 1.606; 95% CI, 1.231 to 2.096; p=0.001), and OS (HR, 3.311; 95% CI, 1.416 to 7.742; p=0.006). In addition, treatment with goserelin resulted in significantly improved LRFS (p=0.039), DMFS (p=0.043), DFS (p=0.036), and OS (p=0.010) in patients aged < 40 years. In patients aged ≥ 40 years, goserelin only improved DMFS (p=0.028) and DFS (p=0.027). Conclusion: Ovarian ablation with goserelin plus TAM resulted in significantly improved therapeutic efficacy in premenopausal patients with stage II/III hormone receptor-positive breast cancer without CIA. [ABSTRACT FROM AUTHOR]

This section considers the treatment options for perimenopausal women with breast cancer. The perimenopause period begins in the so-called stage 2 of menopausal transition (early menopausal transition, where the length of the cycles changes by 7 days or more) and ends after 12 months of amenorrhea. It is characterized by an early increase in follicle-stimulating hormone and is associated with the presence of anovulatory cycles, irregular periods, and loss of menstrual cycles. The recommended treatment is tamoxifen (TAM) with or without ovarian ablation for 2 or 3 years followed by a re-evaluation. TAM should be maintained if the patient is premenopausal and aromatase inhibitors (AI) are recommended once the menopausal status is confirmed. Ovarian suppression is an acceptable adjuvant therapy in those patients with hormone-sensitive tumors. AI should only be used in postmenopausal women or in combination with chemical castration in premenopausal women. This supplement paper includes the key points of roundtable presentations and discussions of hormonal therapy in breast cancer. [ABSTRACT FROM AUTHOR]

To report an unanticipated pregnancy during ovarian ablation treatment with goserelin (10.8 mg SC every 12 weeks) in a 26-year old female with breast cancer. Review of the current literature and reports in MEDLINE, PubMED, and EMBASE using searches with keywords 'goserelin, pregnancy, breast cancer, breast neoplasms, fertility, ovarian ablation, gonadotropin releasing hormone agonists/analogs, leuprolide, pregnancy complications, teratogens' (July-September 2010). Only 3 other reports of failures with goserelin administration at ablative doses in breast cancer patients were discovered. For physicians and breast cancer patients using a GnRH analog, it is important to be aware of the possibility of inadequate ovarian function suppression and the potential for pregnancy. [ABSTRACT FROM AUTHOR]

Summary: Luteinising hormone releasing hormone agonists (LH-RHa) induce ovarian suppression in premenopausal women that is usually reversible on cessation of therapy. They act by binding to pituitary LH-RH receptors, resulting in down regulation of receptors and subsequent suppression of luteinising hormone and estradiol. LH-RHa are effective in the treatment of advanced breast cancer in premenopausal women but their role as adjuvant treatment of early breast cancer is still controversial. Approximately 60% of tumors in premenopausal women are hormone sensitive and these patients are candidates for hormonal treatment. Tamoxifen for 5years is considered the standard endocrine therapy for all premenopausal women with hormone sensitive breast cancer. There is no definitive evidence of additional benefit associated with the use of LH-RHa administered as an alternative or in addition to tamoxifene. In this review we discuss available data on the role of LH-RHa alone or in combination with tamoxifen; on the role of LH-RHa in combination with aromatase inhibitors; and on the potential role of LH-RHa as a strategy to preserve ovarian function during adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Surgical or medical ovarian ablation is likely to be the treatment of choice at the current time, radiation ablation (RA) can be still a reasonable alternative. The efficacy and toxicity of radiation therapy (RT) for ovarian function suppression in 118 premenopausal breast cancer patients were retrospectively evaluated. The median age was 39 years (range 21–52 years). RT was given with either Co-60 or 15MV photons of the linear accelerator. The median total dose was 15Gy in 4 consecutive fractions (range 5Gy single fraction–36Gy in 18 fractions over 3.5 weeks). The endpoint for treatment efficacy was menstrual status. Amenorrhea was noted in 113 of 118 patients (96%) in 6 months following RA. Five patients (4%) who had still normal menstrual functioning after 6 months of RA underwent estradiol and follicle stimulating hormone measurements and were found to have premenopausal levels. No acute Grade 3 or 4 (according to the Radiation Therapy Oncology Group radiation morbidity scoring criteria) toxicities were noted. With a median follow-up of 24.5 months (range: 6–167), no late severe complications that could be attributable to RT were reported. RA should be considered as an option for endocrine responsive premenopausal breast cancer patients and can be easily delivered when postoperative or palliative irradiation is given. [Copyright &y& Elsevier]

Abstract: This contribution focuses on hormone therapy for breast, endometrial and prostate cancer. [Copyright &y& Elsevier]

Introduction International Breast Cancer Study Group (IBCSG) Trial 11-93 is the largest trial evaluating the role of the addition of chemotherapy to ovarian function suppression/ablation (OFS) and tamoxifen in premenopausal patients with endocrine-responsive early breast cancer. Methods IBCSG Trial 11-93 is a randomized trial comparing four cycles of adjuvant chemotherapy (AC: doxorubicin or epirubicin, plus cyclophosphamide) added to OFS and 5 years of tamoxifen versus OFS and tamoxifen without chemotherapy in premenopausal patients with node-positive, endocrine-responsive early breast cancer. There were 174 patients randomized from May 1993 to November 1998. The trial was closed before the target accrual was reached due to low accrual rate. Results Patients randomized tended to have lower risk node-positive disease and the median age was 45. After 10 years median follow up, there remains no difference between the two randomized treatment groups for disease-free (hazard ratio = 1.02 (0.57–1.83); P = 0.94) or overall survival (hazard ratio = 0.97 (0.44–2.16); P = 0.94). Conclusion This trial, although small, offers no evidence that AC chemotherapy provides additional disease control for premenopausal patients with lower-risk node-positive endocrine-responsive breast cancer who receive adequate adjuvant endocrine therapy. A large trial is needed to determine whether chemotherapy adds benefit to endocrine therapy for this population. [ABSTRACT FROM AUTHOR]

Abstract: GABG-IV B-93 is a prospective, randomised study comparing goserelin (n =384) with no further treatment (n =392) in hormone receptor (HR)-negative breast cancer patients (n =465) after 3 cycles cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for patients with 0–3 positive lymph nodes (LN) or 4 cycles epirubicin, cyclophosphamide (EC) followed by 3 cycles CMF for patients with 4–9 positive LN. After completion of the ZEBRA trial the study was amended to enrol also HR-positive patients with 1–9+LN (n =311). After a median follow-up of 4.7 years neither HR-negative nor HR-positive patients showed a benefit for goserelin. The adjusted estimated hazard ratio for event-free survival in HR-negative patients was 1.01 (goserelin versus control, 95% confidence interval [CI] 0.72–1.42, P =0.97) and 0.77 in HR-positive patients (95% CI 0.47–1.24, P =0.27). These results do not support the general use of goserelin after adjuvant chemotherapy in this group of premenopausal patients. [Copyright &y& Elsevier]

Adjuvant ovarian function suppression is acknowledged today as effective therapy for premenopausal patients with early breast cancer. Various modalities have been applied to achieve this treatment option: • First, early investigations comparing ovarian ablation with chemotherapy identified similar outcomes in terms of patients’ rates of disease-free survival (DFS). • Second, prospective randomized trials have more recently focused on luteinizing hormone-releasing hormone analogues (LHRHa) that induce medical ovarian suppression and avoid the morbidity and irreversibility associated with surgical ovariectomy or irradiation. These trials analyzed the value of treatment with goserelin or other LHRHa, with or without tamoxifen, as against chemotherapy. Goserelin was subsequently established as a valid alternative, and our own results demonstrated that goserelin + tamoxifen is more effective and better tolerated in hormone-responsive patients. • Third, other multiple-arm studies have compared LHRHa + chemotherapy with chemotherapy alone. Addition of tamoxifen to goserelin + chemotherapy was shown to improve DFS, and significant benefits in goserelin-treated patients were seen irrespective of use of chemotherapy or tamoxifen. • Finally, ongoing trials are addressing the appropriate duration of LHRHa therapy and other unresolved issues. In summary, combined ovarian suppression with adjuvant goserelin and tamoxifen is considered to be at least as effective as chemotherapy in premenopausal breast cancer patients. Published reports have demonstrated that ovarian suppression is a safe means of reducing risk of recurrence in estrogen receptor-positive women and underlined its use as a competitive alternative to chemotherapy in this patient subset. [ABSTRACT FROM AUTHOR]

Abstract: Gonadotrophin-releasing hormone analogues were investigated as adjuvant treatment for patients with node-negative, hormone-sensitive, premenopausal breast cancer. Patients were randomised to either three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy (n =378) or goserelin every 28d for 2years (n =393). During a median follow-up of 4.9 years, 123 events were observed. The first-failure event of CMF versus goserelin, respectively, was ipsilateral locoregional recurrence (18 versus 20), contralateral breast cancer (7 versus 6), distant failure (35 versus 24) and death without recurrence (2 versus 2). Forty-two (23 versus 19) deaths of any cause occurred. The estimated adjusted hazard ratio for goserelin versus CMF (intention-to-treat analysis) was 0.79 (95% CI=0.54–1.14; P =0.19). It is concluded that medical ovarian ablation with goserelin represents a valid option for premenopausal patients with node-negative breast cancer. [Copyright &y& Elsevier]

Abstract: The Zoladex In Pre-menopausal Patients (ZIPP) study was designed to determine whether addition of goserelin (‘Zoladex’) and/or tamoxifen to adjuvant therapy (radiotherapy and/or chemotherapy), provided benefit to pre- or peri-menopausal women with operable, early breast cancer. A combined analysis of four randomised trials using a core protocol was performed. Patients (n =2710) were randomised into a 2×2 factorial trial based on goserelin and tamoxifen (n =1800) or randomised to receive goserelin or not (n =910; some received elective tamoxifen) for 2 years. The analysis presented here compares women who did (n =1354) or did not (n =1356) receive goserelin. After a median follow-up of 5.5 years, goserelin provided a significant benefit for event-free survival (hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.69, 0.92; P =0.002) and overall survival (HR 0.81; 95% CI 0.67, 0.99; P =0.038). Goserelin was well tolerated. These data show that the addition of goserelin to standard adjuvant therapy is more effective than standard therapy alone in pre-menopausal women with early breast cancer. [Copyright &y& Elsevier]

Abstract: This contribution focuses on hormone therapy for breast, endometrial and prostate cancer. [Copyright &y& Elsevier]