Local Therapy and Survival:
The effect of local therapy (surgery and radiation therapy) on the survival of patients with breast cancer has been debated for a long time. Improved screening and increased use of early local-regional treatment (surgery and radiation) and adjuvant treatment (chemotherapy, hormonal therapy, and trastuzumab) have been associated with a marked reduction in mortality associated with breast cancer. The risk of recurrence is associated directly to the tumor stage. Over 25% of all metastases occur more than 5 years after the initial diagnosis. We know that surgery, even in the early stages of breast cancer, does not cure every woman.How a breast cancer cell metastasizes? In order for a cancer cell to spread, it must have the capacity to migrate and invade through the basement membrane and gain access to the vasculature or lymphatics from the primary site. Upon arrival to a distant organ the cancer cell must have the ability to disrupt and “hijack” the organ to be able to form a macroscopic metastasis.
Metastasis: Once the cancer cells go through the basement membrane of the breast duct they can colonize the blood and lymphatic vessels of the breast and migrate to other parts of the body.
Theories On How Cancer Spreads:
Three theories of why cancers spread have been postulated as possible mechanisms of metastasis.
The first one, postulated in the first half of the 20th century by Halsted, proposed that breast cancer begins as strictly a local disease and tumor cells spread over time in a contiguous manner away from the primary site through the lymphatics. Metastases were considered a direct extension of local involvement. Halsted’s theory postulated aggressive local therapy and even justification for radical breast surgery.
The second hypothesis, which was developed in the 1970’s, was called the systemic theory. This theory arose in view of numerous cases of distant metastases, despite adequate local control with local surgery. Dr. Bernard Fisher postulated the view that breast cancer is a systemic disease that can be divided in two groups: tumors that have the ability to spread to distant sites and those that lack this ability. If distant metastasis were destined to develop, such metastasis had already occurred at the time of diagnosis of the breast tumor. This theory postulated local control and recurrence would have little effect on survival.
The third hypothesis dictates that breast cancer is a heterogeneous disease. Some breast cancers will remain local throughout their course while others have already spread systemically when first detected. In the middle of the group we have those breast cancers that start locally and eventually develop metastases if left untreated. Unfortunately, we generally do not know if metastases have already settled in by the time of diagnosis. The higher the likelihood the tumor was diagnosed at its local stage the higher the likelihood that local therapy (surgery, radiation) will influence survival. The higher the likelihood of metastases at the time of diagnosis the higher the likelihood of benefit from systemic therapy.
Recent data supports the third hypothesis as there is evidence that mammographic screening reduces breast-cancer mortality. The death rate from breast cancer has decreased by 24% from 1990 to 2003. Thus, in some patients earlier diagnosis can prevent the development of distant metastases. Also, recent evidence supports a link between local control and overall survival of breast cancer.