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
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
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
1. Overgaard M, Hansen P, Overgaard J, et al: Postoperative
radiotherapy in high-risk premenopausal women with breast cancer who
receive adjuvant chemotherapy. N Engl J Med 337:949-955, 1997.
2. Ragaz J, Jackson S, Nhu Le I, et al: Adjuvant radiotherapy and
chemotherapy in node-positive premenopausal women with breast cancer.
N Engl J Med 337:956-962, 1997.
3. Hankins J, Miller J, Salcman M, et al: Surgical management of lung
cancer with solitary cerebral metastasis. Ann Thorac Surg
4. Flanigan RC, Blumenstein BA, Salmon S, et al: Cytoreduction
nephrectomy in metastatic renal cancer: The results of Southwest
Oncology Group Trial 8949 (abstract 3). Proc Am Soc Clin Oncol
5. Zellars R, Hilsenbeck S, Clark G, et al: Prognostic value of p53
for local failure in mastectomy-treated breast cancer patients. J
Clin Oncol 18:1906-1913, 2000.
6. Jager J, Volvics L, Schouten L, et al: Loco-regional recurrences
after mastectomy in breast cancer:Prognostic factors and implications
for postoperative irradiation. Radiother Oncol 50(3):267-275, 1999.
7. Haffty B, Toth M, Flynn S, et al: Prognostic value of DNA flow
cytometry in the locally advanced recurrent, conservatively treated
breast cancer patient. J Clin Oncol 10:1839-1847, 1992.