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      Management of menopausal symptoms and ovarian function preservation in women with gynecological cancer

      , , ,
      International Journal of Gynecologic Cancer
      BMJ

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          Abstract

          Gynecological cancers affect a growing number of women globally, with approximately 1.3 million women diagnosed in 2018. Menopausal symptoms are a significant health concern after treatment for gynecological cancers and may result from oncologic treatments such as premenopausal bilateral oophorectomy, ovarian failure associated with chemotherapy or radiotherapy, and anti-estrogenic effects of maintenance endocrine therapy. Additionally, with the growing availability of testing for pathogenic gene variants such as BRCA1/2 and Lynch syndrome, there is an increasing number of women undergoing risk-reducing oophorectomy, which in most cases will be before age 45 years and will induce surgical menopause. Not all menopausal symptoms require treatment, but patients with cancer may experience more severe symptoms compared with women undergoing natural menopause. Moreover, there is increasing evidence of the long-term implications of early menopause, including bone loss, cognitive decline and increased cardiovascular risk. Systemic hormone therapy is well established as the most effective treatment for vasomotor symptoms and vaginal (topical) estrogen therapy is effective for genitourinary symptoms. However, the role of hormone receptors in many gynecological cancers and their treatment pose a challenge to the management of menopausal symptoms after cancer. Consequently, the use of menopausal hormone therapy in this setting can be difficult for clinicians to navigate and this article aims to provide current, comprehensive guidance for the use of menopausal hormone replacement therapy in women who have had, or are at risk of developing, gynecological cancer to assist with these treatment decisions.

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          Most cited references79

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer

            Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a BRCA mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of BRCA mutation status is unknown.
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              Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer

              Data are limited regarding the use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma. In an international, phase 3, placebo-controlled trial, we assessed the efficacy of veliparib added to first-line induction chemotherapy with carboplatin and paclitaxel and continued as maintenance monotherapy in patients with previously untreated stage III or IV high-grade serous ovarian carcinoma. Patients were randomly assigned in a 1:1:1 ratio to receive chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Cytoreductive surgery could be performed before initiation or after 3 cycles of trial treatment. Combination chemotherapy was 6 cycles, and maintenance therapy was 30 additional cycles. The primary end point was investigator-assessed progression-free survival in the veliparib-throughout group as compared with the control group, analyzed sequentially in the BRCA -mutation cohort, the cohort with homologous-recombination deficiency (HRD) (which included the BRCA -mutation cohort), and the intention-to-treat population. A total of 1140 patients underwent randomization. In the BRCA -mutation cohort, the median progression-free survival was 34.7 months in the veliparib-throughout group and 22.0 months in the control group (hazard ratio for progression or death, 0.44; 95% confidence interval [CI], 0.28 to 0.68; P<0.001); in the HRD cohort, it was 31.9 months and 20.5 months, respectively (hazard ratio, 0.57; 95 CI, 0.43 to 0.76; P<0.001); and in the intention-to-treat population, it was 23.5 months and 17.3 months (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). Veliparib led to a higher incidence of anemia and thrombocytopenia when combined with chemotherapy as well as of nausea and fatigue overall. Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear. (Funded by AbbVie; VELIA/GOG-3005 ( clincialtrial.gov number, .)
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                Author and article information

                Journal
                International Journal of Gynecologic Cancer
                Int J Gynecol Cancer
                BMJ
                1048-891X
                1525-1438
                March 01 2021
                March 2021
                March 2021
                October 30 2020
                : 31
                : 3
                : 352-359
                Article
                10.1136/ijgc-2020-002032
                33127864
                cc974863-2169-46d1-9d6b-73b5ada50418
                © 2020
                History

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