Preventing recurrence in young breast cancer patients

Preventing recurrence in young breast cancer patients

11 Dec 2014

Breast cancer patients who retained ovarian function after chemotherapy benefited by ovarian suppression, either with tamoxifen or with aromatase inhibitor. Their benefit was in terms survival without disease, and was shown in a clinical trial.

In particular, after a median follow-up of 5.6 years:

• Patients treated with tamoxifen alone had a disease-free survival (DFS) of 84.7% compared with 86.6% with the addition of ovarian suppression.
• Patients who retained ovarian function had a statistically significant 22% reduction in the DFS hazard with the addition of ovarian suppression to tamoxifen and
• Patients who retained ovarian function had a 35% reduction in the hazard when treated with the aromatase inhibitor exemestane (Aromasin) and ovarian suppression.

Exemestane plus ovarian suppression proved especially effective in women younger than 35, Prudence Francis, MD, of Peter MacCallum Cancer Center in Melbourne, Australia, reported here at the San Antonio Breast Cancer Symposium.

"A practice-changing study"

"I believe this is a practice-changing study," Francis said during a press briefing. "It doesn't answer every question that we had in the premenopausal woman, but for me in my clinical practice, when I see a young women with hormone-sensitive breast cancer, I will now know how to advise that woman."

The results were published simultaneously in the New England Journal of Medicine.

Adjuvant tamoxifen has been recommended for premenopausal hormone receptor-positive breast cancer for the past 15 years. The potential benefits of ovarian suppression in women taking adjuvant tamoxifen remained unclear. The American Society of Clinical Oncology has endorsed a clinical guideline that does not support routine use of ovarian suppression with tamoxifen in premenopausal women.

Chemotherapy-induced ovarian suppression is associated with a reduced risk of breast cancer recurrence, but ovarian suppression results in amenorrhea less often in younger premenopausal patients, the authors noted in the journal article.

Trials with premenopausal women with HR-positive early breast cancer: details

In 2003, the International Breast Cancer Study Group launched two randomized, phase 3 trials to evaluate ovarian suppression in addition to adjuvant endocrine therapy (tamoxifen or exemestane) for premenopausal women with hormone receptor-positive early breast cancer. Francis presented results from SOFT (Suppression of Ovarian Function Trial).

Primary eligibility criteria for this trial included premenopausal status, operable breast cancer, and tumors that expressed estrogen or progesterone receptors in at least 10% of cells. Mastectomy (total or partial) with optional radiation therapy or breast conserving surgery with radiotherapy was allowed, and axillary lymph node dissection or sentinel node biopsy was required.

Patients who did not receive chemotherapy were randomized within 12 weeks after definitive surgery. Patients who did receive chemotherapy before randomization but remained premenopausal were enrolled within 8 months of completing chemotherapy and after laboratory confirmation of premenopausal estradiol level.

Investigators randomized patients to one of the following 3 study arms:

1. tamoxifen alone,
2. tamoxifen plus ovarian suppression, or
3. exemestane plus ovarian suppression.

For ovarian suppression, investigators could choose among triptorelin, bilateral oophorectomy, and bilateral ovarian irradiation.

The primary endpoint was disease-free survival, defined as the interval from randomization to breast cancer recurrence, invasive contralateral breast cancer, second invasive cancer (other than breast), or death without recurrence or second cancer. Secondary endpoints included the time without breast cancer recurrence, time to distant recurrence, and overall survival.

Data analysis

Data analysis included 3,066 patients:

1. 1,021 in the tamoxifen arm
2. 1,024 in the tamoxifen-ovarian suppression arm
3. 1,021 to exemestane and ovarian suppression.

The patients had a median age of 43, 46.7% had received no chemotherapy prior to randomization, and 53.3% had received chemotherapy but remained premenopausal afterward. About 1/3 of patients had node-positive disease.

During follow-up, 299 patients (14.7%) had recurrent disease, a second invasive cancer, or died. The 1.9% absolute difference in 5-year disease-free survival between the tamoxifen groups represented a nonsignificant 17% reduction in the hazard ratio.

In the patients who remained premenopausal after chemotherapy, those randomized to tamoxifen alone had a 5-year rate of freedom from recurrence of 78.0%. In the tamoxifen-ovarian suppression group, the 5-year rate of freedom from recurrence was 82.5% increasing to 85.7% with exemestane plus ovarian suppression.

The trial included 350 women younger than 35, and 233 were included in the primary analysis. In that subgroup, the 5-year freedom from breast cancer was 67.7% with tamoxifen alone, 78.9% with tamoxifen plus ovarian suppression, and 83.4% with exemestane plus ovarian suppression. The difference between the tamoxifen-alone and exemestane groups constituted a 50% reduction in the relative risk of breast cancer recurrence.

More than 95% of premenopausal women who received no chemotherapy prior to randomization remained free of breast cancer at 5 years in all three groups.

"We are going to modify our approach for women younger than 35 with ER-positive tumor"

Edith Perez, MD, of the Mayo Clinic in Rochester, Minn., agreed that the trial has practice-changing potential.

"In the U.S., we have used tamoxifen as our standard," Perez told "MedPage Today". "Now we are going to modify our approach and say if a woman is younger than 35, has an ER-positive tumor and we want to recommend chemotherapy, then in that setting we would consider adding ovarian suppression and exemestane."

Source: MedPage Today