Monday, June 16, 2008

More chemo

Current non-surgical treatments for breast cancer can be broken into 3 categories (at least I see them as 3 different categories). Systemic chemotherapy, endocrine (hormonal) therapy and targeted therapy.

Systemic therapy is the classic chemotherapy you probably know and is what Linda went through for 6 cycles of TAC. Current research in this area is trying to discover which cancers cells are more susceptible to which kind of chemotherapy. Not all cancer cells are alike and certain markers in the cell can help determine which drug cocktail works best, if at all. Because chemotherapy is the most disruptive of the treatments to the rest of the body, it makes sense to only follow a regimen, if any, that has the best odds of success.

Endocrine, or hormonal therapy takes advantage of certain receptors on the cancer cell. Some cancer cells 'feed' on estrogen and progesterone. Cells that behave in this way are known as ER+ and PR+. Tamoxifen is a drug taken daily in pill form, usually for up to 5 years after initial therapy. To the cancer cell, it looks a lot like estrogen. The estrogen receptors on the cancer cell get blocked up by this 'low powered' artificial estrogen hormone. Because the receptors are blocked by this fake, the cell can't feed on real estrogen and the cancer cell ultimately dies. Although Tamoxifen and similar drugs have side effects generally related to a women's internal chemistry (bone loss, hot flashes etc), the side effects are not nearly as life disrupting as chemotherapy and can therefore be taken for a long-term insurance policy against the cancer coming back. About 75% of breast cancers are ER+/PR+.

Targeted therapies are where the huge advancements in cancer drugs are currently being made. As little as 10 years ago, a woman who was Her2+ had a significantly worse prognosis than one who was Her2-. These types of cancer cells, which have an amplification of the Her2 gen, are typically resistant to both chemo and hormonal therapies. There wasn't really a treatment option for them. Today however, thanks to our understanding of the human genome, Herceptin is a drug that was developed to specifically target the Her2 gene (I won't pretend to know exactly how it works, but you can Google it and see what a change it has made in breast cancer treatment). About 20% of breast cancers are Her2+. Leading edge research is discovering other genetic 'defects' in cells that can be exploited to kill off the cell or halt cell growth. Understanding how cancer cells acquire oxygen and cutting off their supply (anti-angiogenesis) is at the forefront of cancer research today.

Understanding the nature of Linda's cancer cell is important to understanding the treatment options. The initial biopsy of the tumor indicated that Linda was ER-,PR+ (15%), and Her2-. A pretty rare combination (remember the Linda 1% factor). This meant that Tamoxifen would have limited effectiveness in long term treatment and Herceptin was not a viable treatment option either. Systemic chemotherapy was our only tool to fight this cancer. As fate would have it, cancer cells like these are very susceptible to chemotherapy which is why we noticed an incredible attack on the tumor in her breast. With such great results, why then did Linda require more chemo? Remember those 2+3 positive lymph nodes? Dr H. said that if the cells in the nodes were the same as those in the breast, she would have expected them to be destroyed too, but they weren't. After further analysis of the pathology, it turns out the cells that were left in the lymph nodes were a bit different than those in her breast. They were ER+ (faint), PR-, Her2-. Did they mutate because of the chemo? Were they different to begin with? It was unclear. Now understand that those nodes were removed during surgery, but there was still a chance that cells of that type had escaped into the bloodstream. Without Tamoxifen or Herceptin as a backup plan, and to increase our odds, we decided that another round of chemo was the right thing to do. There was a good chance that with the original chemo, the lumpectomy and node removal, the cancer had already been eradicated from her body, but if a secondary chemo treatment could push the odds in our favor, even just a bit, then it was a worthwhile thing to do.

I talk like 'we' had a choice, where in reality it was Linda's decision. I am in awe of her resilience and strength, not only to fight for herself, but if you know her, you know she is fighting for our entire family. She fights so that I have a wife and that our kids have a Mom. For that, I am eternally grateful and love her unconditionally.

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