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RADIATION THERAPY IS NOT ROUTINELY NECESSARY
IN THE TREATMENT OF EARLY BREAST CANCER
by Richard A. Evans, M.D.
1011 Augusta Drive, Suite 207
Houston, Texas 77057-2015
OFFICE: (713) 975-6270
FAX: (713) 977-2716
KEY WORDS: BREAST CANCER, PARTIAL MASTECTOMY, EXCISION, MARGINS, LOCAL RECURRENCE, RADIATION THERAPY
Abstract
Background: Breast-conserving surgery is gaining acceptance in the treatment
of early breast cancer. Nevertheless, some patients undergo mastectomy because
they fear local recurrence or have problems related to radiation treatment. It
is now the official position of the National Cancer Institute and the American
College of Radiology that all patients treated with breast-sparing techniques
receive postoperative radiation therapy.
Methods: The entire surgical literature dealing with breast-sparing surgery
without radiation therapy was reviewed and analyzed. This included four
randomized trials and five retrospective studies. No data were deliberately
excluded.
Results: All authorities agree that radiation therapy does not improve the
survival of patients with breast cancer. While the narrow margins of lumpectomy
result in a 40% local recurrence rate for patients with tumors of up to 4 cm,
partial mastectomy alone -- a wider surgical excision -- achieves local
recurrence rates of 9% - 18% in patients with early disease -- lesions 2 cm or
less. Careful patient selection has been shown to reduce local recurrence still
further. For patients with small tumors treated with partial mastectomy the
addition of radiation therapy improves recurrence rates very little and does not
prolong survival.
Conclusions: It is illogical for physicians to insist that radiation therapy be administered to all patients treated with partial mastectomy. Partial mastectomy without routine radiation therapy should be a treatment option for selected patients with early breast cancer. Women should understand that radiation does not improve the survival of patients with this disease. I am aware of no additional studies currently in progress which are designed to clarify this matter.
RADIATION THERAPY IS NOT ROUTINELY NECESSARY
IN THE TREATMENT OF EARLY BREAST CANCER
During the past decade breast-conserving (or conservative) surgery
has been gaining wider acceptance in the treatment of breast cancer. During the
late 1980's and early 1990's, 10% to 45% of patients with stage I disease
underwent conservative surgery.(1),(2),(3),(4) In the United
States this usually involves tumor excision and postoperative radiation therapy.
The NSABP lumpectomy trial (B-06) is largely responsible for this change.(5) Eight years
after treatment, lumpectomy with or without radiation therapy resulted in an
overall survival rate of 71%. This was similar to the survival of patients
treated with modified radical mastectomy. These survival rates were equivalent
despite great differences in the rates of local recurrence. Patients treated
with lumpectomy alone had a local recurrence rate of 40%, while those treated
with lumpectomy and postoperative radiation therapy had a local recurrence rate
of only 10%. These recurrence rates are widely quoted to support the need for
routine radiation therapy following lumpectomy.
Many women with early breast cancer are still treated with total removal of the breast. Some fear local recurrence. Some decline breast-sparing surgery because radiation facilities are not readily available. Others do not wish to undergo weeks of radiation treatment, and for some the cost of radiation therapy may also be a factor. This paper surveys the results of breast-conserving surgery without radiation therapy. Since most patients with breast cancer present with lesions, which are 2 cm or less, this paper is limited to primary tumors of this size.(6) Consequently many of the local recurrence rates presented here are lower than the widely quoted figures. For example, patients in the NSABP trial with tumors less than 2 cm had a local recurrence rate of 27%, not the more familiar 40%, which included some patients with lesions as large as 4 cm.
Since 1988 nine studies have been published in which patients have been
treated with breast-sparing surgery with no postoperative radiation therapy.
These studies are listed in Table I in their order of publication. Table II
lists the local recurrence rates from each study, as well as the margins of
excision and the percentage of patients with pathologically positive lymph
nodes.
The Effect of Surgical Margin on Local Recurrence
In the NSABP lumpectomy trial breast cancers were excised with a narrow margin of excision, often 1 cm or less. Many breast cancers have a stellate appearance on mammogram. Strands of tissue radiate from the primary lesion for a distance that often exceeds the diameter of the tumor. When the surgical excision passes close to the tumor, it may pass through strands of tumor cells. This often results in local recurrence. When the surgical excision approaches 2 cm most of these strands can be excised, and the local recurrence rate is much lower.
Wide excision of the tumor was first employed by George Crile Jr., who called the procedure a partial mastectomy. He was the first surgeon to use surgery alone without adjuvant radiation therapy as the definitive treatment of breast cancer. This treatment is still practiced at the Cleveland Clinic.
Tables I and II include 1,680 patients treated since 1957 with tumor excision alone. All these institutions initiated programs of breast-conserving surgery. These data were acquired prospectively. Only four are randomized trials comparing lumpectomy with and without radiation therapy: the NSABP, Milan, Princess Margaret Hospital, and Uppsala-Örebro, Sweden trials. Two of these studies reported some of the highest rates of local recurrence (NSABP - 27% and University Hospital Uppsala-Örebro, Sweden - 18%). This was caused by the narrow margins of excision used in these trials. Investigators in Uppsala-Örebro were surprised by their high local recurrence rate in a recent analysis of their experience. They speculated that as more hospitals were added to their study, the admission criteria were relaxed. They added that some patient may have had "overlooked multifocality on preoperative mammograms, margins of surgical excision that were too narrow, and less extensive pathological examination of the specimens that resulted in incomplete removal of multifocal disease."
The Roswell Park Cancer Institute reported a 13% local recurrence rate. This
was probably high, because 22% of the patients had pathologically positive lymph
nodes on axillary dissection. The institutions with the lowest rates of
recurrence, the Royal Marsden Hospital (11%), the Cleveland Clinic (11%), the
University of Miami (10%) and Milan (9%) emphasized wide excision and meticulous
surgical technique.(7) These
institutions have clearly demonstrated that recurrence rates of 10% can be
obtained in selected patients with surgery alone -- partial mastectomy.
The Effect of Local Recurrence on Survival
Most investigators now agree that local recurrence following the conservative surgery of breast cancer is not a grave prognostic sign.(8),(9),(10) Indeed, none of the investigators listed in the tables below has found local recurrence to be a survival hazard.
In the NSABP lumpectomy trial postoperative radiation reduced local recurrence from 40% to 10%, but failed to enhance survival. In 1991 investigators at the University of Texas M.
D. Anderson Cancer Center reviewed their experience with local recurrence
following limited excision and radiation. They concluded that the survival risk
of locoregional failure following breast conservation was so small that more
than 10,000 patients would need to be monitored for more than 10 years to detect
any survival deficit.(11) Since the
only benefit of radiation therapy is to reduce local recurrence, it is prudent
to determine if local control can be achieved by partial mastectomy in selected
patients.
Factors Which Influence Local Recurrence
The investigators cited here point out several factors that influence recurrence rates after surgery: the size of the primary tumor, the margins of excision (both width and pathological status), the lymph node status, the patient's age, the presence of carcinoma in situ or extensive intraductal disease, tumor grade, expression of the c-erbB-2 (HER-2/neu) oncogene or the p53 tumor suppressor gene, and invasion of tumor into blood vessels, nerves or lymphatic vessels. Many of these studies included patients with one or more of the above risk factors. All of the institutions except the Uppsala-Örebro Breast Cancer Study and the Princess Margaret Hospital treated some patients with positive nodes. If patients are very carefully selected, utilizing more of the criteria mentioned above, it should be possible to achieve local recurrence rates of 10% or less.
If local recurrence were a great survival hazard, then the added security of
radiation might be justified, but postoperative radiation therapy does not
improve survival. I have previously offered an explanation for the behavior
of locally recurrence breast cancer following limited surgery.(12),(13),(14) This
suggestion has not been challenged.
Radiation Therapy
The long term risks of radiation therapy have not been completely defined. It
will be several more years before the NSABP lumpectomy trial has data from the
second decade after treatment. Nevertheless, the side effects and complications
of radiation therapy have been minimized with improved radiotherapy techniques.
Early changes in the post-irradiated breast include redness and edema, followed
by variable degrees of fibrosis.(15) Boice et
al. reported that radiation therapy for breast cancer does slightly increase the
risk of a second cancer in the opposite breast among young women.(16) Earlier
investigations did not reach this conclusion.(17),(18) The
elimination of routine radiation reduces the small risk of radiation-induced
cancer, and saves radiation therapy for later use to treat a recurrence.
Consensus Conferences
In June 1990 the National Institutes of Health Consensus Development Conference on the Treatment of Early-Stage Breast Cancer concluded that "Although local control can be obtained in some patients with local excision alone, no subgroups have been identified in which radiation therapy can be avoided."(19) None of the authors listed in the tables below were included on the consensus development panel or its planning committee. Only Dr. Umberto Veronesi was a speaker at the conference.
In 1992, the American College of Radiology, the American College of Surgeons, the College of American Pathologists and the Society of Surgical Oncology published "Standards for Breast Conservation Treatment." This twenty page paper also strongly emphasizes the role of radiation therapy. The last section is entitled,"Area for Further Research."Among the eleven questions is,"Are there patients for whom breast irradiation can be omitted?" The implied answer is,"Today, none." The paper has 43 references in the bibliography. None of studies listed in the tables below was included in the bibliography of the paper from the American College of Radiology.
I disagree with the recommendations of these conferences. I also disagree
with their goal to achieve a single treatment upon which most or all of the
panelists can agree. Consensus conferences should strive to achieve a wide range
of alternatives -- practice parameters. The treating physicians can then
consider the wishes of the patient.
Conclusion
Many surgeons recommend partial mastectomy alone for many of their patients with tumors 2 cm. Cady et al. have concluded that selected patients with very small invasive breast cancers can be treated with breast preservation which includes no radiation and no axillary dissection.(20) In England over one-third of surgeons treat their patients with wide tumor excision and no postoperative radiation therapy.(21) Surgeons in Austria and Italy have successfully treated elderly patients with tumor excision and Tamoxifen.(22),(23)
Patients should understand that recent studies demonstrate that
promptly-treated local recurrence is not a life threatening complication.
Radiation therapy does not prolong the survival of patients with this disease.
Recurrent disease can often be treated with reexcision, if sufficient breast
tissue remains. It is reasonable to consider partial mastectomy alone for
selected patients whose tumors can be excised with a wide,
pathologically-negative margin. Patients with extensive intraductal component,
positive axillary lymph nodes, vessel invasion or other risk factors may be less
suitable candidates for surgery alone. Patients should be fully aware of the
principles presented here. Many should be offered a range of prudent treatment
options. Patients should be encouraged to participate in this important decision
about their care and allowed to choose the treatment that is right for them.
Patients who receive all of their advice from advocates of routine adjuvant
radiation do not obtain a balanced view of this debate.
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