LH-RH analogues in the treatment of young women with early breast cancer: Long-term follow-up of a phase II study

Abstract

Abstract. To prevent premature ovarian failure (POF), high-risk, premenopausal women with early breast cancer were given a luteinizing-hormone releasing hormone (LH-RH) analogue during adjuvant chemotherapy. After an adriamycin-based regimen, patients received radiation therapy concomitant with cyclophosphamide, methotrexate and 5-fluorouracil. An aromatase inhibitor was given to patients positive for the estrogen receptor (ER + ). The median age was 43 years (range, 26-45). Among 200 consecutive patients, 46% had no axillary node, and 54% had a mean of 5.4 positive nodes (range, 1-25); 56% were ER + , 44% were estrogen receptor negative (ER -), 13% were triple negative, and 20 had tumors positive for the oncogene, c-erb-B2 (identified with fluorescent in situ hybridization). After a median follow-up of 105 months (range, 65-180), no patient under 40 years old exhibited POF, while 44% of patients over 40 years old exhibited POF. Eight pregnancies were recorded: 7 at term and 1 voluntary interruption. The 10-year disease-free survival and overall survival rates were 85 and 91%, respectively. These data showed that, in premenopausal patients with early breast cancer, the addition of an LH-RH analogue to adjuvant chemotherapy was well tolerated, prevented POF, and was associated with excellent disease-free survival and overall survival rates. IntroductionBreast cancer in young women is associated with a poor prognosis; in the absence of adjuvant treatment, approximately half of the patients will die of metastatic disease. Ovarian ablation was the first described form of endocrine therapy for treating advanced breast cancer (1). Previous trials have also suggested that ovarian ablation with surgery or radiation therapy could reduce the risk of recurrence in young premenopausal women (2). However, in recent years, adjuvant chemotherapy has become the standard treatment for young premenopausal patients with breast cancer that have a high risk of systemic disease (3).One important aspect of chemotherapy is the toxicity, which can induce premature ovarian failure (POF). POF was reported in 68% of women after cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) regimens, and a POF higher rate was observed in women treated with anthracycline-based regimens (4). This may be a serious problem for young women in reproductive ages. Preserving fertility during adjuvant chemotherapy has been an ongoing endeavor, since 1987 (data on file), when a nulliparous, just married, 33-year-old woman, with high risk of breast cancer underwent anthracycline-based adjuvant chemotherapy. She was treated with buserelin, a luteinizing-hormone releasing hormone (LH-RH) agonist, once daily in a nasal spray, during 6 months of chemotherapy. After chemotherapy and radiation therapy, she completed two full term pregnancies.In the following years, we conducted a clinical trial in premenopausal patients with early breast cancer, where another LH-RH agonist, goserelin was given subcutaneously (3.6 mg) every 28 days for 1 year, in addition to adjuv...

Gonadotropin‐releasing hormone agonists for ovarian protection during cancer chemotherapy: systematic review and meta‐analysis

“…Most studies that were observational, non‐randomized or in which oral contraceptives were used were excluded at the abstract screening phase (Figure ). Of the 11 articles that were excluded after full‐text review, two were retrospective studies, two were registered but not completed (NCT02483767 and NCT02430103), one included oral contraceptives in the control group, one was not randomized, two recruited historical controls, one did not include controls and two presented partial results of studies published later in complete version.…”

Temporal influence of endocrine therapy with tamoxifen and chemotherapy on nutritional risk and obesity in breast cancer patients

“…A study with women with BC in CT found an immediate reduction of ovarian blood flow after treatment, demonstrating a postmenopausal profile for most patients accompanied by related symptoms [60]. Thus, those perimenopause women who do CT, especially with anthracycline-based regimens compared to CMF [61], may enter menopause more frequently with CT and present earlier and induced symptoms already known from climacteric, such as changes in body composition [62, 63].…”

Fertility Preservation Using GnRH Agonists: Rationale, Possible Mechanisms, and Explanation of Controversy

“…1,4-9,13-15,19-37 Therefore, this noninvasive and inexpensive treatment has gained ubiquitous interest and popularity. 1,4-9,13-15,19…”