Comment in:
The incidence of lung carcinoma after surgery for breast carcinoma with and without postoperative radiotherapy. Results of National Surgical Adjuvant Breast and Bowel Project (NSABP) clinical trials B-04 and B-06.
Deutsch M, Land SR, Begovic M, Wieand HS, Wolmark N, Fisher B.
Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
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BACKGROUND: In the current study, the authors compared the incidence of subsequent primary lung carcinoma in patients with breast carcinoma who received radiotherapy as part of their treatment and in those patients who did not. The patients were participants in two large National Surgical Adjuvant Breast and Bowel Project (NSABP) breast carcinoma trials, B-04 and B-06, which prospectively randomized women to either undergo surgery alone or to undergo surgery and postoperative radiotherapy. METHODS: The NSABP trial B-04 (1971-1974) randomized patients to undergo radical mastectomy versus total (simple) mastectomy and radiotherapy to the chest wall, axilla, and supraclavicular and internal mammary lymph node areas. For patients with a clinically uninvolved axilla, there was a third randomization arm: total mastectomy without radiotherapy. The B-06 trial (1976-1984) randomized patients between those undergoing total mastectomy versus lumpectomy versus those undergoing lumpectomy and breast irradiation, with all patients undergoing an axillary lymph node dissection. The records of all patients who developed a recurrence in the lung or a new primary lung tumor were reviewed to determine the incidence and laterality of confirmed and probable primary lung carcinoma. RESULTS: For the 1665 evaluable patients on the NSABP B-04 trial (mean follow-up of 21.4 years), there was a total of 23 subsequent confirmed and probable ipsilateral or contralateral primary lung carcinomas. In those patients who had received comprehensive postmastectomy radiotherapy, there was a statistically significant increase in the incidence of these new primary tumors (P = 0.029). With regard to the development of confirmed new primary ipsilateral lung carcinoma alone, the incidence was statistically significantly increased (P = 0.013) in those patients who had received radiotherapy as part of their treatment, and when confirmed and probable ipsilateral lung carcinomas were analyzed, there was a strong trend toward a statistically significant increase in those patients who had received radiotherapy (P = 0.066). For the 1850 evaluable patients on the NSABP trial B-06 (mean follow-up of 19.0 years), there was a total of 30 second primary lung carcinomas but no increase in either ipsilateral or contralateral primary tumors of the lung in those patients who had received radiotherapy. CONCLUSIONS: Extensive postmastectomy irradiation of the chest wall and regional lymphatic node areas, with consequent exposure of a greater volume of lung to higher doses as administered in the NSABP B-04 trial compared with postlumpectomy breast irradiation in the NSABP B-06 trial, was associated with an increased incidence of subsequent primary lung tumors, both ipsilateral and contralateral. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11655
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Cardiovascular death and second non-breast cancer malignancy after postmastectomy radiation and doxorubicin-based chemotherapy.
Woodward WA, Strom EA, McNeese MD, Perkins GH, Outlaw EL, Hortobagyi GN, Buzdar AU, Buchholz TA.
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
PURPOSE: To assess the incidence of long-term toxicity after postmastectomy radiation and doxorubicin-based adjuvant chemotherapy. METHODS: Records of 470 patients treated with mastectomy, doxorubicin-based chemotherapy, and postmastectomy radiation in five institutional prospective trials were retrospectively reviewed. Actuarial toxicity rates were compared with those of 1031 patients treated with mastectomy and doxorubicin-based chemotherapy who did not receive postmastectomy radiation. For those treated with radiation, the chest wall received a median dose of 55 Gy with Co-60 (42%) or electrons (51%). Adjuvant chemotherapy consisted of a doxorubicin-based regimen, often followed by 2 years of cyclophosphamide, methotrexate, and fluorouracil. RESULTS: Median follow-up was 10 years. The overall 10-year actuarial rates of RTOG toxicity Grade >1 and >or=3 after radiation were 4% and 2%, respectively. The overall 10- and 15-year actuarial rates of second non-breast cancer malignancy were 3.8% and 7%, respectively. There was no statistical difference between the rates of non-breast cancer second malignancy in the radiated and unirradiated cohorts (3.4% vs. 4.7% 10-year actuarial rates). Increasing age and treatment with >10 cycles of chemotherapy were associated with higher rates of second malignancy (p = 0.025, p = 0.016). The 10-year actuarial rate of death from myocardial infarction (MI) was 2.4% (eight events) and 0.5% (five events) in the radiated and unirradiated groups, respectively (p = 0.058). Of the 8 irradiated patients who died of MI, 2 patients had left-sided breast cancer. CONCLUSIONS: We found very low rates of serious sequelae after postmastectomy radiation, including death from myocardial infarction and non-breast cancer second malignancy. The rate of second non-breast cancer malignancy was increased among patients treated with >10 cycles of cyclophosphamide-containing chemotherapy.
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Interactions between radiation and endocrine therapy in breast cancer.
Schmidberger H, Hermann RM, Hess CF, Emons G.
Klinik fur Radioonkologie, Georg-August-Unversitat Gottingen, Robert-Koch-Str 40, 37075 Gottingen, Germany.
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Adjuvant radiotherapy and adjuvant endocrine therapy are commonly given to patients with invasive breast cancer or with ductal carcinoma in situ (DCIS). Although both therapies have been well established through a number of randomized studies, little is known about a possible interaction of both treatment modalities if they are given simultaneously. A number of in vitro studies have indicated that tamoxifen treatment might reduce the intrinsic radiosensitivity of MCF-7 breast cancer cells. Conversely, estradiol treatment increases the intrinsic radiosensitivity of MCF-7 cells. In one available animal study, an antagonistic effect of tamoxifen and ionizing radiation (XRT) could not be observed. Retrospective analyses of randomized clinical studies have not indicated an antagonistic effect of tamoxifen on the effectiveness of XRT, since local control has been consistently higher when XRT was combined with tamoxifen, compared with treatment with XRT alone, regardless of whether tamoxifen was started simultaneously with radiotherapy or after completion of radiotherapy. Currently there are no clinical data available that would suggest an adverse effect of adjuvant tamoxifen treatment started prior to or simultaneously with radiotherapy in breast cancer or DCIS. However, since an antagonistic effect of tamoxifen and simultaneous chemotherapy has been reported recently, the issue of simultaneous versus sequential radiation and tamoxifen treatment in breast cancer should be addressed in further studies.
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Comment in:
Limited-field radiation therapy in the management of early-stage breast cancer.
Vicini FA, Kestin L, Chen P, Benitez P, Goldstein NS, Martinez A.
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48072, USA.
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BACKGROUND: Several phase III trials have demonstrated equivalent long-term survival between breast conserving surgery plus radiation therapy and mastectomy in patients with early-stage breast cancer but have not provided information on the optimal volume of breast tissue requiring post-lumpectomy radiation therapy. Therefore, we examined the 5-year results of a single institution's experience with radiation therapy limited to the region of the tumor bed (i.e., limited-field radiation therapy) in selected patients treated with breast-conserving therapy and compared them with results of matched breast-conserving therapy patients who underwent whole-breast radiation therapy. METHODS: A total of 199 patients with early-stage breast cancer were treated prospectively with breast-conserving therapy and limited-field radiation therapy using interstitial brachytherapy. To compare potential differences in local recurrence rates based on the volume of breast tissue irradiated, patients in the limited-field radiation therapy group were matched with 199 patients treated with whole-breast radiation therapy. Match criteria included tumor size, lymph-node status, patient age, margins of excision, estrogen receptor status, and use of adjuvant tamoxifen therapy. Local-regional control and disease-free and overall survival were analyzed using the Kaplan-Meier method, and the statistical significance of differences between treatment groups was calculated using the log-rank test. All statistical tests were two-sided. RESULTS: Median follow-up for surviving patients was 65 months (range = 12-115 months). Five ipsilateral breast failures (i.e., recurrences) were observed in patients treated with limited-field radiation therapy. The cumulative incidence of local recurrence was 1% (95% confidence interval [CI] = 0% to 2.8%). On matched-pair analysis, the rate of local recurrence was not statistically significantly different between the patient groups (1% [95% CI = 0% to 2.4%] for the whole-breast radiation therapy patients versus 1% [95% CI = 0% to 2.8%] for the limited-field radiation therapy patients; P =.65). CONCLUSIONS: Limited-field radiation therapy administered to the region of the tumor bed has comparable 5-year local control rates to whole-breast radiation therapy in selected patients.
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Radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery in postmenopausal women with stage I breast cancer: a decision analysis.
Punglia RS, Kuntz KM, Lee JH, Recht A.
Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA, USA.
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PURPOSE: To compare outcomes for hypothetical cohorts of postmenopausal patients with estrogen receptor-positive tumors that are < or = 2 cm in size, with pathologically uninvolved axillary nodes, treated with radiation therapy plus tamoxifen versus tamoxifen alone after breast-conserving surgery. METHODS: A Markov model was used to simulate patients' clinical course and estimate overall survival, recurrence-free survival, time with an intact breast, and death from breast cancer. Probabilities were derived from randomized trials and retrospective studies. Analyses were performed separately by age of diagnosis in 5-year increments from 50 to 80 years. Sensitivity analyses tested the stability of radiation benefit. RESULTS: The modeled recurrence-free survival benefit of giving radiation therapy was 3.35 years for women who were 50 years of age at diagnosis, versus 0.61 years for women who were 80 years of age. In the 50-year-old cohort, radiation therapy resulted in additional 0.60 years survival, compared with 0.04 years among 80-year-olds. A 50-year-old woman who received radiation therapy plus tamoxifen was less likely to die from breast cancer than if she received tamoxifen alone (2.43% v 5.29%; relative-risk reduction, 54%). An 80-year-old woman had a 1.17% chance of dying from breast cancer if she received radiation therapy plus tamoxifen, versus 2.02% with tamoxifen alone (relative-risk reduction, 42%). Sensitivity analyses showed that the magnitude of benefit was strongly influenced by including unequal rates of developing distant disease after breast recurrence between the treatment arms and varying rates of local recurrence. CONCLUSION: The absolute and relative benefits of radiation therapy and individual patient preferences for different health states should be considered when selecting treatment.
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Integration of systemic therapy and radiation therapy for patients with early-stage breast cancer treated with conservative surgery.
Recht A.
Department of Radiation Oncology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA,USA.
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There is no consensus on the optimal combination of systemic therapy and radiation therapy for patients with early-stage breast cancer treated with conservative surgery. This article reviews prospective and retrospective studies that shed light on this topic. Patients with positive, close, or unknown microscopic margins appear to benefit from relatively early initiation of radiation therapy, whereas those with wider tumor-free margin widths do not. For patients at high risk of distant failure (such as those with = 4 positive axillary nodes), chemotherapy may be more effective when it begins before radiation therapy rather than after. Regimens of concurrent radiation therapy and chemotherapy tend to have higher acute and subacute complication rates than sequential regimens, but the actual rates vary substantially with the exact details of the overall treatment program. There are no data on the impact of the timing of tamoxifen administration on the effectiveness of radiation therapy. Tamoxifen does not appear to increase complication rates relative to the use of radiation therapy alone. Thus, the best way of giving combined-modality therapy is uncertain. Further retrospective and prospective studies to investigate the issues discussed herein should be performed.
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National surgical adjuvant breast and bowel project update: prevention trials and endocrine therapy of ductal carcinoma in situ.
Vogel VG, Costantino JP, Wickerham DL, Cronin WM.
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213-3180, USA.
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Following up on the results of recent completed trials, several major breast cancer prevention trials are either underway or impending. In the Study of Tamoxifen and Raloxifene trial, eligible women are at least 35 years of age and postmenopausal, with either lobular carcinoma in situ or a 5-year risk of invasive breast cancer of at least 1.67%. The study will compare the ability of 5 years of tamoxifen or raloxifene to reduce the incidence of breast cancer. Subjects are randomly assigned to receive either 20 mg of tamoxifen or 60 mg of raloxifene daily. After 3 years of recruitment, 13647 women have been randomized (20.7% of those eligible). The median age of randomized women is 58 years (mean age, 58 years), and their median 5-year risk of breast cancer is 3.3% (mean 5-year risk of breast cancer, 4.0%). Hysterectomy was reported by 52.5% of the randomized women; lobular carcinoma in situ was reported by 8.4% of subjects before randomization. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 trial, 1804 women with ductal carcinoma in situ were randomly assigned tamoxifen after lumpectomy and radiation therapy. Women in the tamoxifen group had fewer breast cancer events at 5 years than did those on placebo (8.2% versus 13.4%, P = 0.0009). The proposed NSABP B-35 trial will have the same design as NSABP B-24 but will compare tamoxifen with anastrozole in postmenopausal women. Outcomes will include both ipsilateral and contralateral new breast cancer and recurrences, as well as the occurrence of regional and distant disease. Enrollment will begin in early 2003.
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Does regional treatment improve the survival in patients with operable breast cancer?
Noguchi M.
Surgical Center, Kanazawa University Hospital, Kanazawa, Japan.
BACKGROUND: The impact of regional therapy on survival of patients with invasive breast cancer remains controversial. Regional therapies discussed include axillary lymph node dissection (ALND), internal mammary node dissection, and locoregional radiotherapy. METHODS: Prospective randomized clinical studies of regional therapy were reviewed using, as a source, Medline, main review articles on the related topic, and statements from consensus conference. RESULTS: Although a number of randomized clinical studies have failed to demonstrate the benefits of regional treatment for survival, it is still a matter of debate whether ALND or regional radiotherapy alone can have a small but significant beneficial effect on the survival of breast cancer patients. However, recent studies have suggested that survival can be enhanced by interaction of postmastectomy locoregional radiotherapy with adjuvant systemic therapy. CONCLUSIONS: Locoregional control is important for enhancing survival in the presence of adjuvant systemic therapy. Although only a few randomized controlled trials show conclusively the survival benefit of local therapies, it is expected that in clinical practice, the node-positive or other high-risk breast cancer patients given systemic treatment will be more frequently treated with postmastectomy radiation.
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Comment in:
Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.
Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N.
National Surgical Adjuvant Breast and Bowel Project, Pittsburgh, PA 15212-5234, USA.
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BACKGROUND: In 1976, we initiated a randomized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer. METHODS: A total of 1851 women for whom follow-up data were available and nodal status was known underwent randomly assigned treatment consisting of total mastectomy, lumpectomy alone, or lumpectomy and breast irradiation. Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained. RESULTS: The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation, as compared with 39.2 percent in the women who underwent lumpectomy without irradiation (P<0.001). No significant differences were observed among the three groups of women with respect to disease-free survival, distant-disease-free survival, or overall survival. The hazard ratio for death among the women who underwent lumpectomy alone, as compared with those who underwent total mastectomy, was 1.05 (95 percent confidence interval, 0.90 to 1.23; P=0.51). The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation, as compared with those who underwent total mastectomy, was 0.97 (95 percent confidence interval, 0.83 to 1.14; P=0.74). Among the lumpectomy-treated women whose surgical specimens had tumor-free margins, the hazard ratio for death among the women who underwent postoperative breast irradiation, as compared with those who did not, was 0.91 (95 percent confidence interval, 0.77 to 1.06; P=0.23). Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer. This decrease was partially offset by an increase in deaths from other causes. CONCLUSIONS: Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained. Copyright 2002 Massachusetts Medical Society
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Tamoxifen--an update on current data and where it can now be used.
Wickerham L.
National Surgical Adjuvant Breast and Bowel Project, Operations Center, Pittsburgh, PA, USA.
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Over the past 30 years, data from a large number of clinical trials have confirmed the efficacy of tamoxifen in estrogen receptor (ER)-positive breast cancer, both as adjuvant therapy and for advanced disease. The 1995 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview of randomized trials of adjuvant tamoxifen versus no tamoxifen showed that during approximately 10 years of follow-up, the proportional reductions in mortality for 1, 2 and approximately 5 years of adjuvant tamoxifen were 12, 17 and 26%, respectively. Tamoxifen is also effective for the prevention of breast cancer. In the National Surgical Adjuvant Breast and Bowel Project (NSABP) breast cancer prevention study (P-1), 5 years of tamoxifen therapy reduced the incidence of invasive and non-invasive breast cancers by 49 and 50%, respectively. In a randomized NSABP trial in women with ductal carcinoma in situ (DCIS), tamoxifen brought about a significant 47% reduction in ipsilateral invasive breast cancers and a 15% reduction in non-invasive breast cancers, compared with placebo. In trials performed by the Swedish Breast Cancer Co-operative Group and the NSABP, the optimal duration of adjuvant tamoxifen therapy appears to be 5 years, although this is equivocal and not yet conclusively defined.
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Patterns of failure in a randomized trial of adjuvant chemotherapy in postmenopausal patients with early breast cancer treated with tamoxifen.
Arriagada R, Spielmann M, Koscielny S, Le Chevalier T, Delozier T, Ducourtieux M, Tursz T, Hill C.
Institut Gustave-Roussy, Villejuif, France.
BACKGROUND: We studied the effect of adjuvant anthracycline-based chemotherapy in postmenopausal patients with resected early breast cancer treated with adjuvant tamoxifen. PATIENTS AND METHODS: The trial included 835 patients with either axillary lymph node involvement, or tumors with histological grade II or III. They were randomized after local surgery to receive either tamoxifen (TAM group) or tamoxifen plus chemotherapy (TAM-CT group) consisting of six courses of 5-fluorouracil, doxorubicin and cyclophosphamide (FAC), or 5-fluorouracil, epidoxorubicin and cyclophosphamide (FEC). Radiotherapy was given after completion of adjuvant chemotherapy in the TAM-CT group and after surgery in the TAM group. RESULTS: The 5-year disease-free survival (DFS) rates were 73% in the TAM group and 79% in the TAM-CT group (log-rank test, P = 0.06). The 5-year overall survival rates were 82% and 87%, respectively (P = 0.06). The 5-year distant metastasis rates were 22% and 16% (P = 0.02), and the 5-year local recurrence rates were 6% and 4%, respectively (P = 0.23). There were no significant differences for contralateral breast cancer or other new primary malignancies. Chemotherapy tended to be more effective for patients who had tumors without estrogen receptors (trend test, P = 0.05). CONCLUSIONS: Anthracycline-based chemotherapy administered to postmenopausal patients receiving adjuvant tamoxifen gave a borderline significant benefit on overall and DFS, mainly by a reduction in distant metastases. Delaying radiotherapy after six courses of chemotherapy did not affect local control after up to 10 years of follow-up.
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Breast cancer recurrences in elderly patients after lumpectomy.
Shah S, Doyle K, Lange EM, Shen P, Pennell T, Ferree C, Levine EA, Perrier ND.
Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Approximately half of breast cancers occur in women 65 years or older. Some studies suggest that breast cancer may be a more indolent disease in this group of patients. Debate exists over the appropriate treatment of these women as they are significantly underrepresented in breast cancer research studies. As a result of comorbid conditions and patient refusal many are often treated less aggressively than their younger counterparts. This study investigated the recurrence rate in elderly breast cancer patients who had undergone lumpectomy as their primary treatment at our institution. A chart review was conducted on breast cancer patients treated from January 1, 1995 through September 26, 2000 with lumpectomy performed at Wake Forest University Baptist Medical Center. Study criteria included female gender and age greater than 65 years, first incidence of breast cancer, no evidence of distant disease at presentation, and availability follow-up assessed by clinical examination and mammogram records. Clinical and pathological features and treatments were evaluated. The Cox proportional-hazards model, Fisher's exact test, and analysis of variance were used for statistical analysis. One hundred thirteen patients met study criteria. The stage distribution was as follows: stage 0 (T(IS)), 16 per cent; stage I, 56 per cent; stage IIA, 24 per cent; and stage IIB, 4 per cent. With a median follow up of 30 months six (5%) patients developed locoregional recurrence, four (4%) developed contralateral cancer, and two patients (2%) developed distant disease. Mean time to recurrence was 21 months. No patient has died of breast cancer, but one patient died of a second malignancy. Radiation therapy and tamoxifen decreased recurrence as compared with no adjuvant treatment or with adjuvant radiation only (P < 0.05). We conclude that patients treated with tamoxifen and radiation therapy had a significantly smaller risk of recurrences than those treated with lumpectomy only or those receiving radiation alone. This supports similar treatment patterns recommended for younger patients. Women over 65 years of age should be carefully evaluated for adjuvant therapy.
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Erratum in:
- Can Fam Physician 2002 Sep;48:1438.
Radiation treatment for breast cancer. Recent advances.
Chow E.
Toronto Sunnybrook Regional Cancer Centre, Department of Radiation Oncology, 2075 Bayview Ave, Toronto, ON M4N 3N5.
OBJECTIVE: To review recent advances in radiation therapy in treatment of breast cancer. QUALITY OF EVIDENCE: MEDLINE and CANCERLIT were searched using the MeSH words breast cancer, ductal carcinoma in situ, sentinel lymph node biopsy, and postmastectomy radiation. Randomized studies have shown the efficacy of radiation treatment for ductal carcinoma in situ (DCIS) and for invasive breast cancer. MAIN MESSAGE: Lumpectomy followed by radiation is effective treatment for DCIS. In early breast cancer, shorter radiation schedules are as efficacious for local control and short-term cosmetic results as traditional fractionation regimens. Sentinel lymph node biopsy is done in specialized cancer centres; regional radiation is recommended for patients with four or more positive axillary lymph nodes. Postmastectomy radiation has been shown to have survival benefits for high-risk premenopausal patients. Systemic metastases from breast cancer usually respond satisfactorily to radiation. CONCLUSION: Radiation therapy continues to have an important role in treatment of breast cancer. There have been great advances in radiation therapy in the last decade, but they have raised controversy. Further studies are needed to address the controversies.
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Radiotherapy for breast cancer: today and tomorrow.
Ryu JK.
Department of Radiation Oncology, University of California, Davis Cancer Center, 4501 X Street, Suite G-126, Sacramento, CA 95817, USA.
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Breast conservation therapy (BCT) with lumpectomy and radiation has allowed many women to preserve their breasts and avoid disfiguring surgery. Lumpectomy and breast irradiation is a standard therapy for early breast cancer patients who desire breast conservation. However, the overall rate of mastectomy exceeds that of BCT in the United States. There have been significant advances in patient awareness of the options available for local management of early breast cancer and changes in the attitudes of physicians, including surgeons, allowing a gradual rise in the rate of BCT in the last two decades. Now, investigations are designed to define subgroups of patients with early breast cancer in whom radiation can be safely omitted. In locally advanced breast cancer, neoadjuvant chemotherapy has allowed some women to have BCT after initial cytoreduction. This approach results in excellent local control when patients are carefully selected for BCT. There is renewed interest in postmastectomy radiation for early breast cancer patients with 1 to 3 positive lymph nodes. In this intermediate risk group for locoregional recurrence, the addition of chest wall and regional lymphatic irradiation to adjuvant systemic therapy has potential for significant improvement in ultimate survival. This concept is novel in breast cancer, a disease that was believed to be systemic at inception and in which only systemic control was thought to impact survival. In this era of effective adjuvant systemic therapy for breast cancer, local control measures have become more important as local control has real potential for impacting survival.
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Local-regional breast cancer recurrence: prognostic groups based on patterns of failure.
Moran MS, Haffty BG.
Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520-8040, USA.
The purpose of this study was to determine the outcome of breast cancer patients sustaining local-regional failure as their first site of relapse in an effort to group patients into prognostic categories. Between January 1970 and December 1992, over 4,000 patients with breast cancer were treated at our facilities with mastectomy or conservative surgery with radiation therapy (CS + RT). Two hundred thirteen patients sustained local-regional relapse without evidence of distant metastasis as their first site of failure, and they served as the population base for this study. The 213 patients with local-regional recurrence of disease were distributed as follows: 68 patients relapsed in the ipsilateral breast following CS + RT within 5 years of original diagnosis (EARLYBR). Fifty-one patients relapsed in the ipsilateral breast after 5 years from original diagnosis (LATEBR). Thirty-five patients relapsed in the chest wall within 5 years following mastectomy (EARLCW). Eighteen patients relapsed in the chest wall later than 5 years following mastectomy, and 41 patients failed in the regional lymphatics following mastectomy or CS + RT (REGREC). Patients with breast relapses were generally treated with salvage mastectomy, and patients with chest wall or regional nodal relapses were treated with radiation to the chest wall, regional nodes, or both. Systemic therapy at the time of local-regional relapse was highly individualized, ranging from observation to tamoxifen to high-dose chemotherapy with transplantation. With a median follow-up of 14 years, the overall 10-year survival for all 213 patients was 61%, and the 10-year distant metastasis-free rate was 59%. Patients with a LATEBR had a relatively favorable prognosis with a 5-year postrelapse distant metastasis rate of 80%. Patients with EARLYBR and LATECW had a similar prognosis, with a 5-year postrelapse distant metastasis rate of 61% and 65%, respectively. Patients with an EARLCW had a 5-year distant recurrence-free rate following a local relapse of 42%. Ten-year survivals from original diagnosis were 62% and 50%, respectively, and distant metastasis-free survival rates were 56% and 52%, respectively. Patients suffering REGREC following mastectomy or CS + RT carried a poor prognosis with a 10-year survival of 33% and a 10-year distant metastasis-free rate of 30%. Patients sustaining local-regional relapse as a first site of failure may be divided into prognostic groups. Patients with LATEBR have a relatively favorable prognosis. Patients with EARLYBR and CWREC have a poorer prognosis with a distant metastatic rate of approximately 50% within 5 years of local-regional relapse. Patients with REGREC have the poorest prognosis. Placing patients with breast cancer and local-regional relapse into these prognostic categories may be helpful in decision making regarding the role of systemic therapy at the time of local-regional relapse.
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Technical factors associated with radiation pneumonitis after local +/- regional radiation therapy for breast cancer.
Lind PA, Marks LB, Hardenbergh PH, Clough R, Fan M, Hollis D, Hernando ML, Lucas D, Piepgrass A, Prosnitz LR.
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
PURPOSE: To assess the incidence of, and clinical factors associated with, symptomatic radiation pneumonitis (RP) after tangential breast/chest wall irradiation with or without regional lymph node treatment. METHODS AND MATERIALS: The records of 613 patients irradiated with tangential photon fields for breast cancer with >6 months follow-up were reviewed. Clinically significant RP was defined as the presence of new pulmonary symptoms requiring steroids. Data on clinical factors previously reported to be associated with RP were collected, e.g., tamoxifen or chemotherapy exposure and age. The central lung distance (CLD) and the average of the superior and inferior mid lung distance (ALD) in the lateral tangential field were measured on simulator films as a surrogate for irradiated lung volume. Many patients were treated with partly wide tangential fields that included a heart block shielding a part of the lower lung. RESULTS: RP developed in 15/613 (2.4%) patients. In the univariate analysis, there was an increased incidence of RP among patients treated with local-regional radiotherapy (RT) (4.1%) vs. those receiving local RT only (0.9%) (p = 0.02), and among patients receiving chemotherapy (3.9%) vs. those not treated with chemotherapy (1.4%) (p = 0.06). According to multivariate analysis, only the use of nodal RT remained independently associated with RP (p = 0.03). There was no statistically significant association between ranked CLD or ALD measurements and RP among patients treated with nodal irradiation with tangential beams. However, there was a statistically nonsignificant trend for increasing rates of RP with grouped ALD values: below 2 cm (4% RP rate), between 2 and 3 cm (6%), and above 3 cm (14%). CONCLUSIONS: RP was an uncommon complication, both with local and local-regional RT. The addition of regional lymph node irradiation slightly increased the incidence of RP among patients treated with the partly wide tangential field technique. Concern for RP should, however, not deter patients with node-positive breast cancer from receiving local-regional RT.
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Breast cancer prevention with selective estrogen receptor modulators: a perspective.
Pritchard KI.
Division of Clinical Trials and Epidemiology, Toronto-Sunnybrook Regional Cancer Centre, Ontario, Canada.
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Chemoprevention for breast cancer is both old and new. It has long been appreciated that early ovarian ablation dramatically reduces the incidence of breast cancer in premenopausal women. It was subsequently demonstrated, in the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) overview, that tamoxifen results in a 40% or greater reduction in the incidence of contralateral breast cancer. Now, the National Surgical Adjuvant Breast and Bowel Project (NSABP) has shown a similar reduction in a randomized trial [Breast Cancer Prevention Trial (BCPT)] comparing tamoxifen and placebo in women aged 35 years or over at increased risk of developing breast cancer because of age, family history, or other factors. In this trial, the incidences of both ductal carcinoma in situ (DCIS) and invasive cancer were reduced. Reduction in incidence was similar over all years of the study and in all subgroups of high-risk women. However, all of the reduction was confined to estrogen receptor (ER)-positive tumors. Raloxifene, a newer selective estrogen receptor modulator (SERM) originally developed for osteoporosis, also appears to have a major preventive effect on breast cancer incidence. Limitations in the design and patient population of raloxifene trials, however, have made it difficult to as yet recommend raloxifene for risk reduction of breast cancer. The randomized Study of Tamoxifen and Raloxifene (STAR) study, which will compare raloxifene to tamoxifen in over 20,000 postmenopausal women at increased risk of breast cancer, as well as ongoing and proposed placebo-controlled studies of tamoxifen, the aromatase inhibitor anastrazole, and other antiestrogens in high- or average-risk postmenopausal women, will provide further results on optimal prevention strategies.
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The role of tamoxifen in breast cancer prevention: issues sparked by the NSABP Breast Cancer Prevention Trial (P-1).
Wolmark N, Dunn BK.
Department of Human Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA.
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The Breast Cancer Prevention Trial (P-1: BCPT) of the National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized 13,388 women, > or = 35 years of age, at increased risk for breast cancer [> or = 1.66% by Gail model criteria or with a history of lobular carcinoma in situ (LCIS)] to 5 years of tamoxifen or placebo. A 49% reduction (P < 0.00001) in invasive breast cancers occurred, 175 with placebo versus 89 with tamoxifen, mainly among estrogen receptor (ER)-positive tumors (130 with placebo vs. 41 with tamoxifen). The major toxicities of tamoxifen were endometrial cancer (15 with placebo vs. 36 with tamoxifen) and thromboembolic disease, both predominantly in women who were > or = 50 years old. Ramifications emerging from the P-1 results regarding the efficacy and toxicities of preventive tamoxifen include the following: (1) Does tamoxifen induce more virulent breast cancers? (2) Does tamoxifen induce more virulent endometrial cancers? (3) Tamoxifen is especially efficacious in reducing breast cancer risk in LCIS (18 invasive breast cancers with placebo vs. 8 with tamoxifen group) and atypical ductal hyperplasia (AH) (23 invasive breast cancers with placebo vs. 3 with tamoxifen). (4) Does tamoxifen reduce breast cancer risk in women at increased risk due to genetic mutations? (5) How can we prevent tamoxifen-resistant breast cancers? (6) What do the BCPT results tell us about who should take preventive tamoxifen? In its ongoing effort to lower the incidence of breast cancer, the NSABP is now implementing its second breast cancer prevention trial, the Study of Tamoxifen and Raloxifene (STAR), which is comparing the two agents with regard to efficacy and toxicity.
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Recurrence rates in patients with central or retroareolar breast cancers treated with mastectomy or lumpectomy.
Simmons RM, Brennan MB, Christos P, Sckolnick M, Osborne M.
Department of Surgery, Weill Medical College of Cornell University, New York Presbyterian Hospital, New York, NY, USA.
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BACKGROUND: Although breast conservation with lumpectomy and radiation treatment has become a commonly used treatment for breast cancer, there are little data to support the use of lumpectomy for central and retroareolar breast cancers. In this study, we investigate the local and distant recurrence rates of patients with central or retroareolar breast cancers treated with lumpectomy compared with mastectomy. METHODS: This study provides a retrospective analysis of 99 patients, from 1981 to 2000, with central or retroareolar breast cancers treated with mastectomy or lumpectomy to determine the frequency of local and distant recurrence. The mastectomy and lumpectomy patients were compared with respect to recurrence and other prognostic factors including: tumor location, tumor size, axillary nodal status, and final surgical margins. RESULTS: The overall frequency of local recurrence was 5 of 99 (5.0%) in the entire group, 3 of 67 (4.5%) and 2 of 32 (6.3%) of patients who underwent mastectomy and lumpectomy, respectively (P >0.99). Overall, 3 patients experienced a distant recurrence as a first event, with 2 patients (3.0%) in the mastectomy group and 1 patient (3.1%) in the lumpectomy group (P >0.99). The type of surgical management was not statistically significant related to either local or distant disease recurrence, with median time to local recurrence of 3.0 years for the mastectomy patients and 5.0 years for lumpectomy patients. Of the patients with central tumors who underwent mastectomy 2 of 42 (4.8%) developed local recurrences compared with those who had a lumpectomy, 1 of 21 (4.8%). Similarly for retroareolar tumors, the local recurrence rate was 1 of 25 (4.0%) for patients undergoing mastectomy and 1 of 11 (9.1%) for those undergoing lumpectomy (P >0.99). CONCLUSIONS: In this study there was no significant difference in local or distant failure rates of those patients with central or retroareolar tumors treated with mastectomy versus lumpectomy. We conclude lumpectomy to be a reasonable treatment option for selected patients with central or retroareolar breast cancers.
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