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Maximizing Radiation Benefit in Breast Cancer

Maximizing Radiation Benefit in Breast Cancer

We read with interest the article and reviews of
"Current Status of Radiation in the Treatment of Breast
Cancer
," which
appeared in the April 2001 issue of ONCOLOGY.[1] These papers suggest that one
of the most controversial areas in this field is the use of radiation in the
management of nodal disease, especially in light of changing surgical
approaches. Several recent articles encourage surgeons to undertake routine
sentinel lymph node dissection for nonpalpable nodal disease in lieu of routine
axillary lymph node dissection.[2,3]

False Node-Negative Rate

Patterns of care should keep up with the science and reduce unnecessary costs
and procedures without increasing patient morbidity or reducing cure rates.
Surgeons have capably undertaken this task by utilizing needle biopsies prior to
surgery. Similarly, sentinel lymph node dissection in lieu of axillary lymph
node dissection enables breast conservation surgery to be performed in an
ambulatory setting, while decreasing false node-negative rates. False
node-negative rates range from 5% to 11% for sentinel lymph node dissection[2,3]
and from 30% to 40% for axillary lymph node dissection.[4] In experienced hands,
the false node-negative rate in sentinel lymph node dissection depends on the
following factors:

  • Techniques used to identify the sentinel node—ie, single or dual
    targeting of nodes.
  • Pathologic approaches used to evaluate the sentinel nodes—ie, number and
    thickness of sections and use of immunohistochemical stains.
  • Pathologic approaches used to evaluate the remainder of the nodes on
    axillary lymph node dissection.

In addition, it should be noted that neither sentinel nor axillary lymph node
dissection evaluates all first-echelon nodes.[4]

Today, systemic adjuvant therapy is the standard of care when the breast
tumor exceeds 1 cm. Hence, sentinel lymph node dissection is most valuable in
T1b, high-grade T1a, and ductal carcinoma in situ (DCIS) tumors, for which being
node-positive will make a difference in adjuvant therapy. Most DCIS and T1a
tumors do not call for nodal evaluation or nodal irradiation.

Nodal Irradiation vs Dissection

Without factoring in the above-mentioned false node-negative rates, there is
a 25% to 40% risk of patients with clinical T1c, N0, M0 tumors being
pathologically node-positive.[2,3] Nodal irradiation at the time of breast
irradiation may eliminate the need for nodal evaluation in many cases without
increasing the cost of radiation therapy. Hence, after local excision, T1c, N0,
M0 tumors need optimal adjuvant radiation to the breast and lymph node chain
along with systemic therapy, without sentinel or axillary lymph node dissection.
Increasing data from several randomized trials and meta-analyses demonstrate
that nodal irradiation improves locoregional tumor control as well as
disease-free and overall survival, with a reduction in cancer mortality.[5-7]

There is a 52% and 71% risk of being pathologically node-positive in patients
with clinical T2, N0, M0 tumors and T3, N0, M0 tumors,
respectively.[3] These patients would best be treated with neoadjuvant and/or
adjuvant chemotherapy, breast conservation without sentinel or axillary lymph
node dissection, and locoregional radiation. Radiation treats the interpectoral
(Rotter’s) nodes and the entire chain of axillary (levels I-III),
subclavicular, and supraclavicular nodes. When indicated, the internal mammary
nodes can also be included in the radiation field.

Axillary lymph node dissection deters radiation therapy to the nodes due to
increased risks of breast and arm lymphedema. However, axillary lymph node
dissection is indicated and therapeutic for palpable nodal disease. Axillary
lymph node dissection after neoadjuvant chemotherapy for nonpalpable nodes is
counterproductive unless it is done for the benefit of a scientific trial. Use
of neoadjuvant chemotherapy refutes the argument that nodal information is
needed to select drug combinations in aggressive breast cancer. In fact, these
patients would be better served with therapy to all the draining nodes rather
than a diagnostic test on some nodes, which subsequently deters adequate nodal
treatment.

With identical axillary control rates,[1] replacing routine axillary lymph
node dissection with nodal radiation saves the patient from a surgical
procedure, which has significant cost and morbidity. Without axillary lymph node
dissection, the breast surgery can be performed without patient admission,
significant rehabilitation, and convalescence.

Conclusions

The challenge for the oncology community is to tailor treatment approaches to
the individual patient’s cancer, so as to increase the patient’s probability
of cure while reducing her physical and psychological morbidity. With many
histopathologic tumor markers now available to predict the behavior of the
breast cancer, the value of nodal evaluation (with its false node-negative
rates) for stratification (in clinical trials), prognosis, and therapy should be
questioned. We need to reconsider the policy that all invasive breast cancers
require identical locoregional treatment.

References

1. Small W Jr: Current status of radiation in the treatment of breast cancer.
Oncology 15:469-488, 2001.

2. Veronesi U, Galimberti V, Zurrida A, et al: Sentinel lymph node biopsy as
an indicator for axillary dissection in early breast cancer. Eur J Cancer
37:455-458, 2001.

3. McMasters K, Tuttle, TM, Carison DJ, et al: Sentinel lymph node biopsy for
breast cancer: A suitable alternative to routine axillary dissection in
multi-institutional practice when optimal technique is used. J Clin Oncol
18:2560-2566, 2000.

4. Lawrence GA: Axillary dissection in invasive breast cancer. Oncology
12:1011, 1998.

5. Whelan TJ, Julian J, Wright J, et al: Does locoregional radiation therapy
improves survival in breast cancer? A meta-analysis. J Clin Oncol 18:1220-1229,
2000.

6. Lawrence GA, Castro P, Collins B: Breast cancer: Systemic benefits of
locoregional treatment. J Clin Oncol 14:1403-1404, 1996.

7. Cuzick J, Stewart H, Rutqvist L, et al: Cause-specific mortality in
long-term survivors of breast cancer who participated in trials of radiotherapy.
J Clin Oncol 12:447-453, 1994.

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