ASCO Breast: Management of Breast Cancer in Young Patients Involves Complicated Surgical, Genetic, and Fertility Issues

Cancer is generally considered a disease of the elderly, but clearly it affects people at all ages. In spite of screening recommendations that now begin only at 50 years of age, breast cancer is often diagnosed in women under the age of 40, and there are specific challenges to management of the disease in this younger population.

In a special session at the American Society of Clinical Oncology Breast Cancer Symposium in San Francisco last week, several clinicians and researchers discussed some of the specific issues that come with cancer diagnoses in younger women.

Image of a breast and axillary nodes by conventional PET scan.

Among the first considerations that arise after an initial diagnosis is that of genetic counseling and testing, as it is possible that a positive BRCA1/2 test could influence initial surgical treatment decisions. Beth Peshkin, MS, CGC, a senior genetic counselor at Georgetown Lombardi Comprehensive Cancer Center in Washington, DC, said that a number of factors go into a decision on whether to undergo genetic testing, including age at diagnosis, family history, and ethnicity.

Generally, any patient diagnosed with breast cancer before the age of 50 is a reasonable candidate for genetic testing, Ms. Peshkin said. BRCA1/2 mutations are associated with 28% risk of contralateral breast cancer after 10 years from an initial diagnosis, and 63% at 25 years, she said; these high risks lead many to choose prophylactic bilateral mastectomy. Notably, mutation carriers also have a substantially increased lifetime risk of ovarian cancer (between 15% and 40%). Testing is expensive, though, at more than $3000 through the test’s patent holder in the United States, Myriad Genetics; insurance does tend to cover most of this cost, however.

Ms. Peshkin also noted that there are a growing number of other gene mutations that are now being tested for, which can shed light on other risks as well; these include p53, PTEN, STK11, and other mutations. “If the patient was interested in genetic testing, these would be among the considerations we would have, but we need to be careful before we send patients down a fishing expedition of expensive and potentially emotionally taxing testing,” Ms. Peshkin said. She added that with improved technology in recent years, “DNA collection is easy, but we still encourage the process be coupled with genetic counseling.”

Surgical decisions

Following any genetic testing and counseling, difficult decisions on surgical approach must be addressed in young patients. Michael Kerin, MD, a professor of surgery at the National University of Ireland in Galway spoke at the session and outlined some of the decisions young patients are faced with. These include assessing the need for mastectomy vs breast conserving surgery, sentinel node biopsy, and MRI.

“We have level 1 evidence that conservative breast surgery in appropriately selected young women gives the same long-term survival as mastectomy,” Dr. Kerin said. “But there is an increased incidence of local recurrence, which comes in at about 1% per year . . . but this does not translate into a survival disadvantage.”

Many women also wonder if young age will influence outcomes. Dr. Kerin pointed to one large study he and colleagues conducted that showed younger women had higher tumor grade, higher stage, lower incidence of lobular carcinoma, higher rate of ER negativity, and higher rate of HER2 positivity; in spite of all this, though, there was similar overall survival between older and younger patients.

Another major area of concern for young women is breast reconstruction after mastectomy. Dr. Kerin said that in his own unit there has been a substantial increase in the use of immediate reconstruction over the last decade, and more recently there has been an increase in the use of implant-only breast reconstruction; latissimus dorsi flap reconstruction with implants was more common in earlier years. There is little evidence available on immediate vs delayed reconstruction, and Dr. Kerin said that immediate reconstruction should be offered as an option to all women.

Pregnancy and fertility issues

“One of the questions we often get from our young cancer survivors is, ‘can I have a baby in the future?’” said Jennifer Litton, MD, an assistant professor of oncology at M.D. Anderson Cancer Center in Houston. She added that it is not possible to obtain level 1 evidence about safety of pregnancy post-diagnosis, as “clearly we cannot randomize people to become pregnant or not after a diagnosis of breast cancer.”

Instead, young survivors concerned about fertility must rely on case control and registry studies, and Dr. Litton said that none of these studies have indicated any survival disadvantage for pregnancy. Interestingly, some have even shown the opposite; a meta-analysis of 14 studies and close to 20,000 women found a relative risk of mortality of 0.59 (95% CI, 0.50-0.70) for pregnancy vs those who did not become pregnant, and found the effect was more significant in women under the age of 35 with node-negative disease.

There is a chance that these studies are limited by the so-called “healthy mother” effect: only those patients who were healthier following the breast cancer diagnosis went on to become pregnant. Some of the studies on the topic have tried to adjust for this effect, but there is a chance it played a role.

The specific treatment used to treat breast cancer can also affect fertility, Dr. Litton said. “We know that when women are exposed to systemic therapy or to radiation therapy that we can shift the natural age of menopause to a younger age,” she said. “And this may be of concern for women who thought they may have more time to try to have a baby.”

ASCO has published a table on the risk of permanent amenorrhea associated with various breast cancer systemic therapies, which Dr. Litton said can be a useful tool in making treatment decisions. Some of the lowest risk therapies include vincristine and methotrexate, while some combinations involving cyclophosphamide carry higher risks of permanent amenorrhea. Recent work on taxanes has suggested there may be little or no increased risk.

Patients concerned about fertility also have nontraditional options including IVF with embryo freezing, ovarian stimulation, oocyte freezing, and other more experimental methods. Of course, other roads to parenthood exist as well, including adoption, surrogacy, and donor eggs.

The management of breast cancer in younger patients clearly presents challenges that do not come up in older populations, but evidence continues to accumulate as to some of the best practices. “Age per se is not an adverse prognostic indicator,” Dr. Kerin said. “Appropriate management of a young woman with breast cancer involves significant multidisciplinary input.”