Gynecologic Oncology Consult

Oophorectomy for premenopausal breast cancer


 

One-quarter of patients with breast cancer are diagnosed at a premenopausal age and these young women may be directed to discuss oophorectomy with their ob.gyn. This may be because of the discovery of a deleterious BRCA gene mutation, which places them at increased risk for ovarian cancer, but oophorectomy may also be a therapeutic option for their breast cancer: 60% of premenopausal breast cancers are hormone receptor–positive. Ovarian ablation has been associated with improved overall survival and disease-free survival among these patients.1

Estrogen is an important promoter of breast cancer and is predominantly derived from ovarian tissue in premenopausal women. However, in postmenopausal women, the majority of estrogen is produced peripherally through the conversion of androgens to estrogen via the enzyme aromatase. Aromatase inhibitors, such as exemestane, anastrazole, and letrazole, are drugs which block this conversion in peripheral tissues. They are contraindicated in premenopausal women with intact ovarian function, because there is a reflex pituitary stimulation of ovarian estrogen release in response to suppression of peripheral conversion of androgens. For such patients, ovarian function must be ablated either with surgery or with gonadotropin-releasing hormone (GnRH) analogues such as leuprorelin and goserelin if aromatase inhibitors are desired.

Dr. Emma C. Rossi, assistant professor in the division of gynecologic oncology at UNC-Chapel Hill.

Dr. Emma C. Rossi

Two major clinical trials, the SOFT and TEXT trials, explored the benefit of ovarian ablation in the adjuvant treatment of early stage premenopausal breast cancer. The SOFT trial included 3,066 women randomized to receive tamoxifen, tamoxifen with ovarian suppression, or an aromatase inhibitor with ovarian suppression.2 In the TEXT trial, 2,672 patients were randomized to receive either an aromatase inhibitor with ovarian suppression or tamoxifen with ovarian suppression.3 Results of the two trials showed that there was greatest treatment effect when ovarian suppression is added to tamoxifen, or in patients receiving an aromatase inhibitor with ovarian suppression. This effect appeared to be dominant among women who had received prior chemotherapy and were at higher risk for recurrence, and who remained premenopausal after completion of their primary therapy. While ovarian suppression was associated with improved disease-free survival, it was not associated with an increased overall survival.

In these trials, ovarian ablation was achieved either reversibly with GnRH analogues or permanently and irreversibly with oophorectomy. No studies have compared the survival benefit of these two approaches; however, surgical ovarian ablation is immediate, reliable, and has been shown to be the most cost-effective method.4 It is a good option for women who struggle with adherence to repeated appointments for injections. It also substantially reduces the risk for ovarian cancer, which is elevated among this population of patients, even among those without a deleterious BRCA gene mutation.

BRCA populations

For women with BRCA germline mutations and a history of breast cancer, oophorectomy is associated with a 70% risk of all-cause mortality, including a 60% reduction in breast cancer mortality. This effect is inclusive of patients with “triple-negative,” hormone receptor–negative tumors. The positive effect on breast cancer mortality is predominantly seen among BRCA-1 mutation carriers, and if the oophorectomy is performed within 2 years of diagnosis.5

Technique

When performing oophorectomy either for breast cancer or because of a hereditary cancer syndrome such as BRCA mutation, it is important to ensure that the ovarian vessel pedicle is transected at least 2 cm from its insertion in the ovary. This prevents leaving a residual ovarian remnant. In order to do this, it may be necessary to skeletonize the ovarian vessels free from their physiological attachments to the sigmoid colon on the left, and terminal ileum and cecum on the right. It is also important to ensure that the ureter is not invested in this more proximal segment of ovarian vessels. To prevent this, the retroperitoneal space can be opened lateral to and parallel with the ovarian vessels, and the “medial leaf” of the broad ligament swept medially to expose the ureter as it crosses the bifurcation of the external and internal iliac arteries at the pelvic brim. With the ureter in view, a window can then be made in the “medial leaf” above the ureter and below the ovary and ovarian vessels, in doing so creating a skeletonized ovarian vessel segment which can be sealed and cut 2 cm or more from its insertion in the ovary.

The fallopian tubes should be removed with the ovarian specimens, with attention made to removing the fallopian tube at its junction with the uterine cornua. It should be noted that the majority of fallopian tube cancers arise in the fimbriated end of the tube, and cornual tubal malignancies are fairly uncommon.

Next Article: