I started out these blogs from San Antonio saying that it did not seem as though there would be any big news out of this meeting. (Note: The â€œnewsâ€ the media cover isnâ€™t always groundbreaking or significant.. What you read and hear about often is influenced more by a companyâ€™s PR efforts than by what is actually scientifically or clinically important.) But I think was wrong.There is definitely a paradigm shift occurring in how we think about breast cancer. For decades, we have assumed that all breast cancer was the same. We thought that, basically, a cell went â€œbadâ€ through a series of chance mutations and then went on to behave like a cancer cell. We tried to determine whether the cancer had spread by looking at the lymph nodes and other characteristics of the cancer, and then we added increasingly more toxic therapy to kill it.
Currently, our thinking is that there are at least five, and maybe more, different subtypes of breast cancer (based on whether the tumor is ER, PR or HER2 positive or negative). In turn, we routinely use targeted treatmentsâ€”giving women with HER2-positive tumors Herceptin and those with ER or PR positive tumors hormone therapyâ€”to treat the subtype of cancer they have. Weâ€™ve also believed that these different tumors types were the result of a process that occurred as a cancer developed. But we may need to rethink this, too!
Thea Tlsty, PhD, a pathologist at the University of California, San Francisco (UCSF) Comprehensive Cancer Center, gave a late-breaking presentation on her work with ductal carcinoma in situ (DCIS). Dr. Tlsty conducted a large, retrospective study of 1460 women who had been diagnosed with DCIS. Of this group of women, 1102 had no subsequent tumors while 358 had a recurrence. Of those, 194 were diagnosed with more DCIS while 164 were diagnosed with an invasive tumor. All of the women had been diagnosed in the 1980s, and the only treatment they had was surgery. Dr. Tlsty tried to figure out if she could identify a group of biomarkers that could predict who had the kind of DCIS that recurred as invasive and who did not.
Ultimately, she was able to identify markers that did pretty well at predicting which DCIS would come back as invasive cancer. But even more interesting was that the biomarkers predicted a subset of breast cancers that we refer to as basal-like tumors, and which are known to be very aggressive. Why is this so exciting? Not only because it would be wonderful to be able to figure out which DCIS needs aggressive treatment and which does not, but also because it says that the different kinds of cancers start way earlier in the precancerous stage. If you are a shy kid you grow up to become a shy adult not an aggressive adult. Similarly, if you are an aggressive DCIS you grow up to be an aggressive tumor! This , in turn, may mean that targeted therapies are as important for treating DCIS as they are for treating invasive cancer!
This new thinking was also highlighted by the Genomic Health presentations, which showed that their Oncotype DX Recurrence Score was as accurate in women with ER-positive tumors and positive nodes as it had been in the women with negative nodes. This does not just mean we have a new test. Instead, it means that nodes are much less important than we thought in dictating which treatment is indicated! Itâ€™s the tumor biology that matters most and should determine treatment strategies.
As Genomic Health reported, the women with a low recurrence score who were node positive benefited from hormonal therapy but not from chemotherapy, whereas the women with a high recurrence score did better with chemotherapy. This means using node status to decide whether a woman should have chemotherapy or hormone therapy is probably not relevant. Whether the cancer has spread to the nodes may be helpful in determining a womanâ€™s prognosis, but it does not appear that itâ€™s an appropriate way to determine treatment. This means that our hypothesis, which had been that if the cancer has spread to the nodes, the more aggressive the treatment has to be, is probably not true.
Against this background the talks about refining the sentinel node technique seemed a little out of date. We are still arguing about what constitutes a positive sentinel node. Do a couple of cells (<.2mm) matter? How about micro (.2-2mm) metastateses? The studies presented here suggested that sentinel node metastases over 2 mm clearly does matter but maybe the others do not. Since most of the women in these studies had been treated with chemotherapy, the findings are difficult to interpret. However, a larger randomized controlled study is underway that will answer this question.
The bigger issue: By the time we get the answer, will it really matter? If the biology determines which treatment is indicated, will nodes be as important as they once were? Stay tuned! The great thing is that we continue to question, explore, and challenge our assumptions in an attempt to make more progress in breast cancer, and that is the fun of San Antonio!