Mark Burkard, MD, PhD
Associate Professor, Medicine
Mark Burkard, MD, PhD
UW Carbone Cancer Center
University of Wisconsin School of Medicine and Public Health
Two years ago, I met a woman who had been living with breast cancer for nearly 4 decades. I saw her for a colleague, who had taken on her case from 2 previous oncologists over the years. I reviewed the most recent imaging, which showed a slight progression in a metastatic mass, indicating the current therapy was no longer working.
Reviewing her chart, I learned she originally had breast cancer in 1978; it recurred in the 1980s, and she had a biopsyproven pelvic metastasis that was treated with radiation but never disappeared. She had received multiple medical treatments over the years, including multiple hormonal therapies and a few chemotherapies. Although she was reaching her eighth decade of life, her performance status remained excellent.
But the day I met her, there was evidence of progression of the metastatic mass, a gradual growth that had occurred very slowly over years. Now this woman, incredibly knowledgeable about her history and the unusual aspects of her cancer, wanted my advice on what to do next. My training and guidelines made it clear that I could select from a number of possibilities, including other chemotherapies considered standard and the more esoteric endocrine therapies she had not yet received.
I recommended observation.
One of the classic papers I assign to oncology fellows is “Natural History of Untreated Breast Cancer” by HJG Bloom.1 It describes a series of women in the 19th century who were not treated for their breast cancer, 4% of whom lived a decade after the breast cancer was found. In 1 case, a woman lived 35 years with breast cancer.
Now I had met a woman who had lived nearly 4 decades with breast cancer that, in retrospect, was not cured despite surgery and adjuvant therapy in the 1970s. Did other women live decades with incurable cancer? After paying careful attention to other unusual case histories and speaking with colleagues, I became convinced that this woman was not alone—others had survived an extreme length of time with incurable breast cancer, although 4 decades remained highly unusual.
In a typical case history, a woman with estrogen receptor–positive lobular breast cancer was treated with surgery and adjuvant therapy and then developed metastasis years later. One woman developed a pancreas mass more than 10 years after primary treatment of lobular cancer. Her physicians were concerned about pancreatic cancer, but the resected mass turned out to be metastatic breast cancer. Further endocrine therapy was provided for a few years. The woman had no evidence of disease for another decade, until she developed lower gastrointestinal bleeding and a biopsy revealed the same cancer invading the colon, 2 decades from initial presentation.
Other patterns became apparent: solitary lung nodules, resected metastatic lesions of nodes, and lesions of the bone with minimal progression over long periods. For example, 1 woman had an ovarian mass treated with hysterectomy and bilateral salpingo-oophorectomy for what was thought to be primary ovarian cancer but was in fact recurrent breast cancer. She remained without evidence of disease for many years, until she developed another lobular breast cancer.
Although the most common—and longest—extreme survivors had hormone-sensitive cancers, we also identified extreme survivors with HER2-positive cancer metastatic for more than a decade, as well as several with indolent triple-negative breast cancer with survival over 5 years. Still, these cases were usually less extreme than the decade-long histories identified with hormone-positive breast cancers.
As I spoke with colleagues, I found it important to be clear what I meant by “extreme survivors.” Many colleagues were familiar with the National Cancer Institute project looking for “extraordinary responders” and expected that I was looking for the same. However, few of my extreme survivors had ever had an extraordinary response to therapy. They had received many therapies with evidence of slow progression. Thus, there was little overlap between extraordinary responders and extreme survivors.