Pam Harrison

May 09, 2017

SAN DIEGO — For premenopausal women with estrogen receptor (ER)-positive breast cancer treated with tamoxifen for 5 years, lifetime outcomes are better with an extra 5 years of tamoxifen than with ovarian ablation followed by aromatase inhibitor therapy or with no additional treatment, new research shows.

"Short-term evidence suggests that aromatase inhibitors have an advantage over tamoxifen, which makes sense because you achieve a greater reduction in estrogen by removing the ovaries and putting women on an aromatase inhibitor," said investigator Janice Kwon, MD, associate professor of obstetrics and gynecology at the University of British Columbia in Vancouver, Canada.

"But when women undergo oophorectomy, they can't go on hormone-replacement therapy because of their ER-positive breast cancer, so they are at risk for bone loss and heart attacks and dying of these consequences much later on," she told Medscape Medical News.

"It's important for gynecologists to appreciate that ovarian ablation is associated with downstream health risks, particularly in young women who have early-stage disease," she added.

To determine the optimal endocrine strategy for premenopausal women treated with 5 years of tamoxifen, Dr Kwon and her colleagues compared three regimens: 5 extra years of tamoxifen, ovarian ablation followed by an aromatase inhibitor, and no additional treatment.

For the study, "we designed a simulation model to estimate the costs and benefits of these three endocrine strategies over a time horizon of 40 years," Dr Kwon reported.

"We extrapolated data from the Nurses' Health Study to estimate the long-term consequences of ovarian ablation in these breast cancer patients," she explained.

They measured effectiveness in years of life expectancy gained.

Table. Treatment Outcomes Predicted by the Model

Average Outcome No Additional Treatment 5 Extra Years of Tamoxifen Oophorectomy Plus Aromatase Inhibitor
Lifetime cost per patient, $ 1074 3550 14,312
Gain in life expectancy, years 16.69 17.71 17.06
Deaths from breast cancer, n 7300 6200 5500


A simulation of treatment-related adverse events for the three strategies predicted that "tamoxifen given for 5 more years would lead to a higher number of endometrial cancer cases and thromboembolic events," said Dr Kwon. It also predicted that "ovarian ablation followed by an aromatase inhibitor would yield a higher number of bone fractures, coronary heart disease events, and strokes."

Although the model predicts that there will be more deaths from breast cancer with 5 extra years of tamoxifen than with ovarian ablation plus an aromatase inhibitor, the long-term consequences of ovarian ablation would add approximately 2000 deaths, she explained.

Long-term Consequences of Oophorectomy

Women who are young when they undergo oophorectomy are at risk because of the long-term consequences of being estrogen-deficient over a lifetime, said Dr Kwon.

Although the majority can be expected to do well, for every eight women who undergo oophorectomy without receiving hormone-replacement therapy, one woman can be expected to die as a result of these long-term consequences, she pointed out.

"But no clinical trial is going to follow these women for 30 years," she told Medscape Medical News.

"We conclude that for premenopausal women with early ER-positive breast cancer who've completed 5 years of tamoxifen therapy, another 5 years of tamoxifen is preferable to ovarian ablation with an aromatase inhibitor as an extended endocrine strategy," she added.

These aren't elderly women we're talking about; these are women in the prime of life.

For a woman with low-grade, early ER-positive breast cancer, the 5-year survival rate is above 95%, "so you are talking already about something that has very good survival," said Jennifer Blake, MD, chief executive officer of the Society of Obstetricians and Gynaecologists of Canada.

Research evaluating the treatment of breast cancer typically lasts no more than 5 years, but physicians clearly need to think in the longer term when survival for this particular group of patients is so prolonged, she explained.

"If you are a 35- or 40-year-old woman, we're talking about getting to age 50, age 60. These aren't elderly women we're talking about; these are women in the prime of life," Dr Blake told Medscape Medical News.

Study after study has shown that premature oophorectomy leads to increased morbidity and mortality, so the observations made by Dr Kwon and her colleagues have been widely validated, she said.

Although this is a modeling study, it was "built on very well-established outcomes and science, so I think it should give us pause and make us at least consider the long-term consequences of what we do today," she concluded.

Dr Kwon and Dr Blake have disclosed no relevant financial relationships.

American College of Obstetricians and Gynecologists (ACOG) 2017 Annual Meeting: Abstract 11OP. Presented May 7, 2017.

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