Researchers suggest treatment protocols should be reassessed

Women with premenopausal breast cancer who are childhood cancer survivors have worse survival outcomes than other women who develop breast cancer before menopause, according to a new study.

This increased mortality is primarily seen in patients who are Hispanic, Asian/Pacific Islander, and younger women, and in those with earlier stage, lymph node-negative, and hormone receptor–positive disease.

“We traditionally use similar therapies for primary breast cancer and second primary breast cancer, and base our treatment approaches on specific prognostic factors,” Candice A. M. Saunder, MD, surgical oncologist at the University of California Davis Comprehensive Cancer Center, California, said in a statement about the study, which appeared in Cancer Epidemiology, Biomarkers and Prevention. “Our results suggest that breast cancer-related survival is significantly decreased among all survivors of childhood, adolescent, and young adult cancer who were treated with radiation therapy and then develop breast cancer, even in the setting of early-stage breast cancer and other characteristics that are considered good prognostic factors. As such, we may need to tailor our treatment strategy for women with a second primary breast cancer.”

Breast cancer occurrence in premenopausal women is typically more aggressive than disease that occurs later in life, Saunders and colleagues pointed out. Their epidemiological study compared primary breast cancer in premenopausal women with secondary breast cancer in premenopausal women who had been treated with radiation for cancer when they were children or young adults.

Radiotherapy is well-established as part of the treatment management of common childhood cancers such as Hodgkin lymphoma, sarcomas, and breast cancer, but “it is also a strong risk factor for a secondary breast malignancy, especially when used to treat patients with childhood of adolescent and young adult cancer,” the researchers wrote. “In addition, it has been shown that for women treated for a primary breast cancer prior to 40 years of age, this risk of secondary malignancy applies not only to the ipsilateral breast but also to the contralateral breast at a much higher rate than their older counterparts.”

Saunder and colleagues noted that secondary breast cancers “are thought to have unique clinical characteristics, as well as distinct gene expression profiles.”

Saunder and colleagues culled their study cohort from the California Cancer Registry and compared 107,751 women diagnosed with primary breast cancer from 1988 to 2014 with 1,147 women of similar age with secondary breast cancer who had been treated with radiotherapy for their primary tumor. They analyzed breast cancer specific survival using Cox proportional hazards regression.

The data acquired from the database included the diagnosis (primary or secondary breast cancer), age at diagnosis, and race/ethnicity, as well as cancer stage, tumor grade, histology, node involvement, estrogen receptor, HER2 status, and sequence of primary cancer.

In the secondary breast cancer cohort (women age 12 to 50), the researchers noted some differences from the primary breast cancer cohort. Those with secondary breast cancers (ages 35-45) were:

  • More often non-Hispanic Black (10.3% versus. 7.4%) or Hispanic (26.4% versus. 22.2%) race/ethnicity, more likely to have earlier stage tumors (stage I, 45.5% versus 33.4%), more likely to be higher grade (grade III, 49.3% versus. 39.5%), more likely to have no lymph node involvement (65.7% versus 53.4%), and more likely to be ER/PR negative (ER, 36.2% versus 22.2%; PR, 41.8% versus 26.8%).
  • Less likely to be treated with chemotherapy (55.4% versus 62.2%) or radiation (26.3% versus 45.5%).
  • More likely to get a mastectomy (63.0% versus 50.2%).

The researchers also found that non-Hispanic Black patients were more likely to have secondary breast cancers than non-Hispanic white women, while Asian/Pacific Islanders were not — OR, 1.35; 95% CI, 1.11-1.66 versus OR, 0.76; 95% CI, 0.63-0.92.

“In addition, secondary breast cancers were more likely to be diagnosed at an earlier tumor size (T3 versus T1a, OR, 0.38; 95% CI, 0.28-0.52) and without lymph node involvement (lymph node positive versus negative, OR, 0.58; 95% CI, 0.51-0.67), but more likely to be ER/PR negative (OR, 1.76; 95% CI, 1.52–2.03) and have a higher grade (grade III versus. I, OR, 1.76; 95% CI, 1.41-2.21),” the study authors wrote.

Saunder and colleagues suggested that, given the data they have found on secondary breast cancers in patients who received radiation during childhood and young adulthood, it might be time to rethink treatment protocols.

“Do smaller and lower stage secondary breast cancers need more aggressive treatment?,” Saunders and colleagues wrote. “Our data show that women with secondary breast cancers are having more aggressive surgical therapy but receiving less chemotherapy or radiation. The cause of this difference in treatment is not directly known, but consideration should be given to the treatments used for the primary cancer, such as chest radiation and prior anthracycline use, that may limit the ability to use them in the secondary setting.”

Limitations of the study include that they could not determine the radiation fields or chemotherapies used. The study authors also noted that they could not determine full treatment details in both cohorts, nor were genetic information or comorbidities delineated.

  1. Women with premenopausal breast cancer who are childhood cancer survivors have worse survival outcomes than other women who develop breast cancer before menopause, according to a new study.

  2. This increased mortality was seen mostly in patients who were Hispanic, Asian/Pacific Islander, and younger women, and in those with earlier stage, lymph node-negative, and hormone receptor–positive disease.

Candace Hoffmann, Managing Editor, BreakingMED™

The study was sponsored by UC Davis Health and a UC Davis Comprehensive Cancer Center Support Grant.

Sauder disclosed no relevant relationships.

Cat ID: 22

Topic ID: 78,22,730,22,691,192,925