The changing philosophies of breast cancer treatment over time can be compared to the swing of a pendulum. At first, the predominant theory was that breast cancer was a local disease requiring local management to result in cure. Unfortunately, increasingly radical surgery still failed to prevent a significant percentage of distant failures.
With this realization, the pendulum swung to the other extreme and the antithetical treatment philosophy arose. This philosophy proposed that breast cancer was a systemic disease that required systemic management to result in cure. Local control was thought to be of little consequence. Clearly, though, this is not wholly correct, since there are breast cancer patients who are cured with local therapy alone.
So with the passage of time, the pendulum continues to swing. However, it no longer reaches either extreme; it swings or rests somewhere in between. Neither philosophy completely dominates.
Survival With Local Control
The importance of systemic therapy is quite evident, but local control may have more of an effect on survival than most recently believed. For example, the postmastectomy radiation trials showed an improved survival with improved local control.[1,2] Also, regarding other disease sites, data now suggest that local control of the primary, even in the setting of frankly metastatic disease, is associated with improved survival.[3,4]
With these lines of evidence, it is difficult to doubt the influence of local control on survival. As evidence mounts supporting the influence of local control on survival, it is increasingly important to achieve one so as to optimize the chance of the other.
Three Steps for Optimum Local Control
The process of maximizing local control has three steps: The first step is to recognize the factors that are associated with an increased risk of local failure. The second step is to use this information to choose a therapy that has the greatest probability of achieving local control. The third and final step is to optimally manage a local failure, should one occur.
In this issue of Oncology, Drs. Freedman and Fowble provide the reader with an excellent review of the incidence and risk factors for local failure after initial treatment of invasive breast cancer, along with a review of the multidisciplinary management of isolated local recurrences. This information allows the reader to follow the three-step process I believe is necessary for optimum local control.
The authors review the risk factors for local recurrence in stage I/II breast cancer patients treated by breast-conserving therapy, and stage IIIIA breast cancer patients treated by mastectomy. They consider the following clinical factors: age, tumor size, multifocal/multicentric disease, and genetic factors; and review the following histopathologic factors: node involvement, extracapsular extension, margin status, extensive intraductal carcinoma, histologic grade, lymphvascular invasion, and gene/oncogene suppression. The authors thoroughly cite the literature relating these factors to local failure. This identification of risk factors is the first step in the process of optimizing local control.
The second step is to use this information to select a therapy that would minimize the chance for a local recurrence. The authors skillfully aid the reader in this process in Table 2, where they compare the two accepted forms of local management of breast cancer (modified radical mastectomy vs breast-conserving therapy) with respect to the putative prognostic value of each of these clinical and histopathologic factors. This treatment-to-treatment comparison of the prognostic value of these factors will aid the reader in selecting a primary therapy that is most likely to result in the best local control. For example, one may be motivated to recommend a mastectomy over breast-conserving therapy if the resected tumor was positive for an extensive intraductal component and had uncertain/positive margins. (The authors correctly point out, however, that if negative margins are obtained in these patients, there appears to be no additional risk of local failure with breast-conserving therapy.)
Our third and final step in maximizing local control is addressed by the authors review of the literature concerning possible treatments of an isolated chest wall or ipsilateral breast recurrence. The prognostic factors of survival after recurrence are also discussed. The authors conclude with a few general treatment recommendations.
There are only two risk factors that would be worthy of addition to the authors list. There is some evidence that would suggest that ploidy and especially S-phase fraction have prognostic value for local failure. In our study, we looked at several putative prognostic factors for local failure in 1,271 mastectomy-treated breast cancer patients. Results showed a significant correlation between high S-phase fraction and local failure; however, this is not a universal finding.
Finally, the authors list prognostic factors of survival after local failure. I would only add to that discussion work by Haffty et al showing that S-phase fraction and ploidy are significant prognostic factors for survival after an ipsilateral breast tumor recurrence.
Drs. Freedman and Fowble have presented a thorough and thoughtful review of the incidence and risk factors of local recurrence in women with breast cancer treated either with mastectomy or limited surgery and adjuvant radiation. The strength of this article lies, in part, in the extensive, cited literature. This list will allow readers to easily research the data supporting or refuting the prognostic value of each of these factors, and allow them to make their own conclusions. The pendulum may continue to swing, but such dominance of either systemic or local management theories will probably never occur again.