Patients with Invasive Secondary Breast Cancer May Have Higher Mortality

Patients who previously received radiotherapy for ductal carcinoma in situ may have higher mortality after developing an invasive second breast cancer.

A study released in the Journal of the National Comprehensive Cancer Network suggested that patients who previously received radiotherapy (RT) for ductal carcinoma in situ (DCIS) had higher mortality after developing an invasive second breast cancer (SBC) than those who did not receive RT.1

This research may influence clinical decision-making regarding initial therapy for DCIS and highlights the importance of a discussion with each patient before treatment, taking into account individual patient characteristics and preferences.

“Our results provide additional factors for [the patients] to consider, especially for younger patients without estrogen receptor (ER) expression, where radiation therapy could limit salvage options in the future if the disease returns,” Rinaa S. Punglia, MD, MPH, Dana-Farber Cancer Institute/Brigham and Women’s Hospital, said in a press release.2

In this cohort of 3,407 patients, prior RT was associated with higher rates of breast cancer specific mortality (HR, 1.70; 95% CI, 1.18-2.45; = .005), even after controlling for cancer stage. This risk trended higher in patients with ipsilateral versus contralateral SBC (HR, 2.07 vs 1.26; = .16). 

Patients with ipsilateral SBC were younger (<.001) and more often lacked estrogen receptor expression (<.001). Researchers noted that one factor likely contributing to the finding of increased mortality associated with ipsilateral SBC after prior RT is that prior radiation to the ipsilateral breast limits subsequent salvage options in the same breast.

Researchers used the National Cancer Institute’s Surveillance, Epidemiology, and End Result (SEER) database to identify patients who received breast-conserving therapy with or without RT for primary DCIS in 2000 through 2013 and subsequently developed a stage I to III invasive SBC within the same time period. Out of those patients, 150 deaths were reported; 89 among those who were initially treated with radiation therapy, and another 61 who were not.

“Our results suggest that patients who develop SBC after prior RT may benefit from intensified or alternative treatment as a strategy to improve survival,” the researchers wrote.

A study published in Cancer in 2012 analyzed the benefit of adding radiation therapy after excision of DCIS. Researchers found that radiation for DCIS is prophylactic; it reduces the risk of invasive recurrence, while also increasing the probability of eventual mastectomy. This research also suggested that personal patient preferences should drive decision-making.3

Breast cancer is the second leading cause of cancer death in women, according to the American Cancer Society. In 2019, it is estimated that about 62,930 new cases of carcinoma in situ will be diagnosed and 268,600 new cases of invasive breast cancer will be diagnosed in women.4


1. Li CP, Zhang Z, Cronin AM, Punglia RS. Mortality After Invasive Second Breast Cancers Following Prior Radiotherapy for DCIS. Journal of the National Comprehensive Cancer Network. doi:10.6004/jnccn.2019.7323.

2. New Research in JNCCN Offers Reassurance about Rarity of Recurrence for Early-Stage Breast Cancer after Breast-Conserving Surgery [news release]. Plymouth Meeting, PA. Published November 25, 2019. Accessed December 2, 2019.

3. Punglia RS, Burstein HJ, Weeks JC. Radiation therapy for ductal carcinoma in situ: A decision analysis. Cancer. doi:10.1002/cncr.26293.

4. American Cancer Society. How Common is Breast Cancer? American Cancer Society Website. Published September 18, 2019. Accessed December 2, 2019.