The brass ring in breast cancer research has always been figuring out a way to personalize treatment so physicians would know exactly what is needed to cure a particular type of cancer. The goal has always been to tailor treatment to each case in order to provide therapies for, and offer various kinds of surgery to, those who would benefit—sparing others from the side effects, both medical and surgical, if they personally had nothing to gain.
In the war against breast cancer, physicians want to leave behind the shotgun approach against cancer cells—bullets shot everywhere at everyone, so normal cells suffer much collateral damage and some individuals derive no benefit. We look forward to the development of a sniper’s rifle with a laser scope and a single bullet that zeroes in precisely on the enemy.
The medical and surgical fronts have seen significant progress toward this goal since the 1970s and 1980s. Our medical oncology colleagues and researchers have discovered and developed targeted agents that have played a major role in increasing survival rates for breast cancer among those for whom these agents are active. Examples of this include—
• tamoxifen, which reduces the risk of dying from breast cancer by 40 to 50 percent in women whose tumors are fed by estrogen (hormone-receptor positive).
• Herceptin, a major advance in treating one of the most aggressive subsets of breast cancer—tumors that overexpress a receptor called Her2/neu. Prior to the development of Herceptin, patients with Her2/neu positive disease (approximately 15 to 20 percent of all patients with breast cancer) had a much poorer prognosis than those who were Her2/neu negative. With Herceptin, which targets the Her2/neu pathway, women with Her2/neu-positive breast cancer can now expect excellent survival rates.
The same advancement has happened in the arena of surgery. Prior to the 1970s and ’80s, the treatment for breast cancer was a radical mastectomy. It was the only option for breast cancer surgery, and one size fit all. This operation, associated with disfigurement, significant limits to range of motion, and a high risk of arm swelling called lymphedema, was the only proven way to get all the cancer out. In the 1980s, as smaller tumors were detected with mammography, leaders in breast surgery conducting clinical trials around the world were able to show that lumpectomy—removing only a small portion of the breast and then giving radiation—provided survival rates equal to those of mastectomy, with minimal risk of recurrence in the breast.
With the advent of breast-conserving surgery, more women had a choice, and the surgical approach was tailored to the size and extent of the individual woman’s cancer. In the 1990s, sentinel node biopsy was developed; this procedure allowed us to check lymph nodes under the arm, usually the first site of cancer spread, without removing them all, thereby performing a much shorter, smaller operation, with fewer long-term risks of lymphedema, for women whose lymph nodes were normal. This more targeted approach spared women with normal lymph notes a larger, more aggressive surgery, while surgeons continued to perform aggressive surgery for those with positive nodes, for whom it was potentially beneficial.
Most recently, a large clinical trial has shown that even in some women with positive nodes, total lymph node removal may not be necessary or beneficial. This is another example of progress in chiseling away and further defining subsets of women who will or will not benefit from more or less surgery. So, in terms of our weaponry, we have moved past the shotgun approach, but have not yet reached the sniper’s rifle.
The research presented in a paper, recently published in Nature by the Cancer Genome Atlas Network, shines a light on some of the many pathways toward the next generation of individualized cancer treatment strategies. This paper demonstrates that cancer is not just one disease, but essentially can be characterized as four different subtypes, each of which behaves biologically differently. By elucidating the mechanisms and complex pathways associated with the different types of breast cancer, we have the potential to take targeted therapy to the next level by identifying new targets. For example, one particular subtype of breast cancer looks remarkably like ovarian cancer from the standpoint of genetic profile. Could this insight mean that perhaps drugs that have traditionally worked in ovarian cancer may be of benefit to this particular subset of breast cancer patients?
In the last decades we have made much progress toward identifying and characterizing the pathways that lead to cancer development, but we also know that we have only just skimmed the surface of potential targeted therapy. A greater and more detailed understanding of what the driving factors are for cancer development will pave the way for designing treatments that specifically target these driving factors. Stay tuned for the next generation of cancer treatments: for each woman with breast cancer, a sniper’s rifle with a laser scope aimed at her particular cancer.