SAN ANTONIO—Even in metastatic breast cancer, a subset of patients achieves long-term survival, and the characteristics of these long-term survivors may provide clues for defeating the disease, researchers suggested here at the San Antonio Breast Cancer Symposium.
Of 181 patients studied, 14 women—or eight percent of the total—survived 10 years or longer, said Pooja Murthy, MD, who performed the study as a resident at the University of Michigan, but is now a hospitalist at Columbia-New York Presbyterian Hospital prior to beginning a fellowship in hematology/oncology at New York University. Nine of those 14 women remain alive.
“We identified younger age at first diagnosis; hormone-positive status—estrogen receptor-positive and progesterone receptor-positive; longer time to progression; and single-organ involvement as significant characteristics of these long-term survivors,” she said in an interview at her poster presentation.
Single-organ involvement didn't necessarily mean just one lesion in the affected organ, she explained. “There could be several liver nodules, but it would still count as just one organ.”
Murthy also pointed out that women with visceral metastases—lesions in the lungs and liver—showed a trend towards doing better than women who had metastases in other organs, although that difference did not reach statistical significance.
But there are always outliers, she and her colleagues reported: For example, one woman was diagnosed at age 66 with Stage 4 HER2-positive breast cancer and was treated for two and a half years with trastuzumab and remains alive 14.4 years later at age 80.
Women who have brain or central nervous system metastases were among the long-term survivors—three of the survivors in the study had brain metastases. One of those women died 10 years after metastatic disease was diagnosed; the second women died 10.4 years after diagnosis of metastases, and the third woman remains alive 13.3 years after the metastasis was discovered.
That third woman was diagnosed with breast cancer when she was 42. Her metastasis was observed two years later, and she has been on trastuzumab therapy for more than nine years, Murphy reported.
“It is very helpful to be able to tell women who are diagnosed with HER2-positive breast cancer that there is a possibility for long-term survival. People hear ‘cancer’ and they think it is a death sentence, but now we can turn this into a chronic disease. This is not a hopeless disease.”
Murthy said she thinks that one of the keys to survival is having the disease confined to one organ. “We think that in these cases, clinicians should attack the cancer vigorously and with indefinite treatment,” she said.
Surgical removal of the metastases was performed mainly in women with brain metastases, not for lesions in the lungs or liver. All of the three long-term survivors in the study who had brain metastases underwent resection of the lesions—“These women only had one brain metastasis,” Murthy said.
In performing the retrospective trial, the researchers were interested in the survival curve ‘tail’—an indication of long-term survival. “HER2-positive metastatic breast cancer is currently considered an incurable disease, with the majority of patients ultimately relapsing within five years. However, emerging evidence suggests that there may be a subset of patients with HER2-positive metastatic breast cancer who have prolonged survival following treatment with HER2-targeted therapy.
The single-institution review of patients diagnosed with HER2-positive metastatic breast cancer covered the years 1990 to 2013. That included 212 patients diagnosed with metastatic disease at the University of Michigan. Of that group, 181 patients who had received at least 21 days of trastuzumab therapy were included in the review.
The researchers looked at overall and progression-free survival as primary endpoints. Women were eligible for the study if they were diagnosed with distant metastatic breast cancer. HER2 status was defined according to institutional guidelines at the time of diagnosis. In addition to trastuzumab treatment, the use of lapatinib was also permitted.
The mean age of the women whose charts were scrutinized was 48. At the time of diagnosis, seven women were classified as having Grade 1 breast cancer; 43 women were diagnosed with Grade 2 breast cancer; and 83 women were diagnosed with Grade 3 breast cancer. In 48 cases, the grade of the tumor was missing from the charts—that represented 26.5 percent of the women in the study.
At diagnoses, 24 women were determined to have Stage 1 breast cancer; 67 had Stage II; 31 had Stage 3, and 46 had Stage 4. Stage data were missing in 13 cases.
The median time to development of metastatic disease was two years, but ranged from zero to 21.2 years. The researchers reported that 92 of the women in the study—50.8 percent of the total cohort—had metastases in multiple areas of the body at the initial discovery of metastatic disease. A total of 59 women—32.6 percent—developed central nervous system metastases at any time during the study.
“Given these data, if you have a woman with these characteristics, you would want to treat her with trastuzumab early, and treat with trastuzumab indefinitely as long as it can be tolerated,” Murthy said. Four of the nine surviving women are being treated with long-term trastuzumab. One of those women has been on the HER2 receptor inhibitor for more than nine years—and counting. The others have been taking trastuzumab for at least five years.
“Many of these long-term survivors were on trastuzumab for many years, and then there were some women who didn't take it for a long time and are still free of disease progression,” Murthy said. “That leads to the question of what is the right duration of treatment for these women. If these people are so responsive to trastuzumab they may be able to take treatment for a short period of time and that would be enough, or do they need to take it long term to continue to suppress the cancer?”
Murthy said that with the development of new drugs such as pertuzumab doctors will have to determine how to integrate these drugs into treatment decisions for women with long-term survivorship.
‘Exquisitely Sensitive to Herceptin’
Asked for her opinion for this article, Ruby Sharma, MD, Attending Physician at North Shore-Long Island Jewish Cancer Institute, said that long-term survivors are part of the experience of many clinicians who treat breast cancer patients.
“We have long-term survivors, but we do not consider them cured. These patients respond to HER-2 targeted therapy with radiological complete response, but they tend to relapse when they're taken off therapy. They are exquisitely sensitive to Herceptin. It is an interesting finding knowing that trastuzumab also has immunomodulatory properties along with HER-2 blocking properties. It makes Herceptin an attractive agent to combine with anti-PD1 drugs for future clinical trials.”
Sharma said that because she can tell patients there is a possibility for long-term remission with continued trastuzumab therapy it would help in compliance issues. “Prolonged Herceptin treatment for metastatic HER-2-positive patients seems to be a suppressive regimen.”