October was Breast Cancer Awareness Month, and I felt totally immersed in a paper storm, an overload of information on the topic. Making my immersion even deeper, while preparing two breast cancer talks, I was also in the thrall of an amazing book, “The Emperor of All Maladies: A Biography of Cancer” by Dr. Siddhartha Mukherjee. When I closed my eyes at night, I had visions of a swirling vortex of tables and graphs.
And as the pages circled around inside my head, I perceived a coherent yet unsettling message: we are doing a rather a poor job of early diagnosis of breast cancer. Yes, mammography saves lives, but estimates are that of the 29% decline in breast cancer mortality over the past 20 years, only 10% (and perhaps less) of the 29% is attributable to screening and early detection.
On 10/24, the Archives of Internal Medicine published an online first paper by H. Gilbert Welch, MD, MPH, and Brittney A. Frankel entitled “Likelihood That a Woman With Screen-Detected Breast Cancer Has Had Her Life Saved by That Screening.” The article basically says that despite the media hype, there is a great overstatement of the lifesaving value of mammography and women diagnosed with breast cancer on mammography do not evidence any improved survival.
While this message is distressing and is creating an enormous amount of anger and angst, the news that is being ignored is that major improvements in survival have accrued because of improved treatment protocols. The shoreline has been completely altered in recent years and bears little resemblance to the cruel sea of cancer treatment that dominated the field when I was in training. Treatment now is far more sophisticated and focused than the “slash-burn-poison” of not so long ago.
There have been two major changes. First, the scale and scope of surgical intervention has receded, moving from the morbid, disfiguring Halstead radial mastectomy to lumpectomy, sentinel node biopsy and other more appropriate conservative procedures. The second shift has been in understanding the regulation of breast cancer, with proteomics helping to direct the development of new drug therapies. Scientific American noted the following: (http://www.scientificamerican.com/article.cfm?id=breast-cancer-treatment-milestones)
1. 1977: Hormone-blocking drug tamoxifen approved in U.S. for treatment of breast cancers sensitive to estrogen or progesterone.
2. 1988: Trial results show that preoperative chemotherapy shrinks tumors, making less invasive surgeries possible.
3. 1997: Letrozole, which blocks estrogen synthesis, approved in U.S. for patients whose cancer did not respond to tamoxifen.
4. 1998: Trastuzumab, the first molecular-targeted cancer therapy, approved in U.S. for use in breast cancer.
5. 2007: Lapatinib, an inhibitor of growth signaling, approved in U.S. for use in breast cancer.
6. 2008: Bevacizumab, an inhibitor of blood vessel formation in tumors, approved in U.S. for use in breast cancer.
These recent drug developments represent the true flowering of “bench to bedside” research in translational medicine. Research focuses on the intersection of assaying for gene signature for a tumor, coupled with receptor testing, techniques that help in selecting the most efficacious treatment modalities. We are at the leading edge of a new wave of clinical care that incorporates genomic testing, minimal residual disease markers, and personalized targeted therapies that maximize benefits while limiting toxicities.