This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Taghian, A. G. Articles by Wolmark, N. Search for Related Content PubMed PubMed Citation Articles by Taghian, A. G. Articles by Wolmark, N.

Low Locoregional Recurrence Rate Among Node-Negative Breast Cancer Patients With Tumors 5 cm or Larger Treated by Mastectomy, With or Without Adjuvant Systemic Therapy and Without Radiotherapy: Results From Five National Surgical Adjuvant Breast and Bowel Project Randomized Clinical Trials

Alphonse G. Taghian, Jong-Hyeon Jeong, Eleftherios P. Mamounas, David S. Parda, Melvin Deutsch, Joseph P. Costantino, Norman Wolmark

From the National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh; Department of Radiation Oncology, University of Pittsburgh Medical Center; Departments of Radiation Oncology and Human Oncology, Allegheny General Hospital, Pittsburgh, PA; Department of Radiation Oncology, Massachusetts General Hospital and Boston Medical Center, Boston, MA; Aultman Cancer Center, Canton; and Northeastern Ohio Universities College of Medicine, Kootstown, OH

Address reprint requests to Alphonse G. Taghian, MD, PhD, Department of Radiation Oncology, Massachusetts General Hospital; 55 Fruit St, Boston, MA 02114; e-mail: ataghian{at}partners.org

	ABSTRACT

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
PURPOSE: Lymph node (LN) –negative breast cancer tumors 5 cm occur infrequently, and their optimal management is not well defined. In this study, we assess patterns of locoregional failure (LRF) in LN-negative patients who underwent mastectomy, either with or without adjuvant chemotherapy or hormonal therapy and without postmastectomy radiation therapy (PMRT).

PATIENTS AND METHODS: Of 8,878 breast cancer patients enrolled onto National Surgical Adjuvant Breast and Bowel Project B-13, B-14, B-19, B-20, and B-23 node-negative trials, 313 had tumors that were 5 cm or larger (median, 5.5 cm; range, 5.0 to 15.5 cm) at pathology and were treated by mastectomy. Median follow-up time was 15.1 years. Therapy included adjuvant chemotherapy in 34.2% of patients; tamoxifen in 21.1%; chemotherapy plus tamoxifen in 19.2%; and no systemic therapy in 25.5%.

RESULTS: Twenty-eight patients experienced LRF. The overall 10-year cumulative incidences of isolated LRF, LRF with and without distant failure (DF), and DF alone as first event were 7.1%, 10.0%, and 23.6%, respectively. Cumulative incidences for isolated LRF as first event for patients with tumors of 5 cm or more than 5 cm were 7.0% and 7.2%, respectively (P = .9). For patients who underwent no systemic treatment, chemotherapy alone, tamoxifen alone, or chemotherapy plus tamoxifen, the incidences were 12.6%, 5.6%, 4.6%, and 5.3%, respectively (P = .2). The majority of failures occurred on the chest wall (24 of 28 patients). Multivariate analysis did not identify significant prognostic factors for LRF.

CONCLUSION: In patients with LN-negative tumors 5 cm who are treated by mastectomy with or without adjuvant systemic therapy and no PMRT, LRF as first event remains low. PMRT should not be routinely used for these patients.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
Patients with node-negative breast cancer and primary tumors 5 cm or larger represent less than 1% of new breast cancer patients,¹ and optimal management for these patients is not well defined. Although standard recommendations for these patients include systemic treatment in addition to surgery, the addition of radiation therapy for improved local control or survival is debatable. The postmastectomy radiation therapy (PMRT) guidelines of the American Society of Clinical Oncology² provide no recommendations for T3N0 tumors because of a lack of information and conflicting data. Yet, the majority of practicing radiation oncologists recommend PMRT for these tumors.³

In this study, we examine the rates and patterns of locoregional failure (LRF) in 313 breast cancer patients whose tumors were 5 cm at pathology and who, per protocol, did not receive PMRT as part of five randomized clinical trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP). These patients underwent axillary lymph node (LN) dissection and were treated with modified radical mastectomy (MRM), with or without adjuvant chemotherapy or adjuvant hormonal therapy.

	PATIENTS AND METHODS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
Study Population
Patients included in this report were treated in five NSABP node-negative trials (B-13, B-14, B-19, B-20, and B-23) evaluating adjuvant chemotherapy and/or hormonal therapy but not allowing for adjuvant PMRT. To be included in this analysis, a patient had to be eligible with follow-up, had to have undergone MRM, and had to have had a pathologic tumor 5 cm in diameter. A brief summary of each of the five trials is provided in Table 1. Treatment details, outcome, and other aspects of each trial have been reported in previous publications (B-13,⁴ B-14,^5,6 B-19,⁷ B-20,⁸ and B-23⁹). All trials were approved by local human investigations committees or institutional review boards in accordance with assurances filed with and approved by the Department of Health and Human Services, when appropriate. Written informed consent was required for participation in the trials.

Time to isolated LRF was defined as time from definitive surgery to the first diagnosis of an isolated LRF. Time to DF was defined as time from surgery to the first DF. Local or regional failures occurring without a subsequent DF but with additional follow-up of less than 4 months were counted as isolated events.

The nonparametric method¹⁰ was used to estimate 10-year cumulative incidence for isolated LRF, LRF ± DF, and DF alone. For the analysis of cumulative incidence for each end point, competing events were defined as (1) any first isolated recurrence, (2) any first other recurrence followed by a DF within 4 months, (3) any first DF, and (4) any death without evidence of previous recurrence. Gray's K-sample statistic was used to test whether any statistical significance of differences existed in cumulative incidence among groups stratified by protocols (univariate analysis).¹¹ The Cox proportional hazards model¹² was used to test the association between cause-specific hazard functions and selected patient and tumor characteristics and to estimate the magnitude of such association, stratified by protocols. All P values were two tailed, and P .05 was considered to be significant. Analyses were based on all follow-up information received at the NSABP Biostatistical Center as of June 30, 2005.

	RESULTS

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
A total of 8,878 node-negative patients enrolled onto these five NSABP trials were eligible with follow-up. Of these, 313 patients met our predetermined criteria and are included in this analysis (Table 1). Patients in this study were treated between 1981 and 1998. Table 2 lists patient and tumor characteristics. Two hundred sixteen and 169 patients were at risk for any first recurrence at 5 and 10 years, respectively. Of the 313 patients considered for this analysis, 28 (8.9%) presented with isolated LRF as the first event. The overall 10-year cumulative incidences of isolated LRF, LRF ± DF, and DF alone as first event were 7.1%, 10.0%, and 23.6%, respectively. The median times to develop isolated LRF and DF were 2.3 and 1.8 years, respectively. The majority of LRFs (62.2%) occurred within the first 4 years, and 18.9%, 10.8%, and 8.1% of LRFs occurred at 4 to 8, 8 to 12, and more than 12 years of follow-up, respectively.

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

The study we carried out was designed to contribute to the base of clinical decision-making knowledge about the use of radiation therapy in node-negative patients with large tumors. We found 169 patients with tumors (T3N0) larger than 5 cm among 8,878 patients enrolled onto five node-negative trials (Table 1), representing less than 2% of node-negative patients. We decided to include patients with 5-cm tumors (large T2N0) to increase the number of patients to 313, which represented 3.5% of LN-negative patients enrolled onto these trials (Table 1). The isolated LRF and LRF ± DF rates were similar whether the tumor was 5 cm or larger than 5 cm (Table 3). Although the total number of patients in this series is relatively small, to our knowledge, because of the infrequency of this clinical scenario, this is the largest series to date on patients with tumors of 5 cm or larger with negative LNs treated by mastectomy without PMRT.

In Finland, Helinto et al¹ identified 38 patients with T3N0 tumors treated by MRM from among 4,190 new breast cancer patients (representing < 1% of the patients). Mignano et al¹³ reported the LRF rate in his series of 101 patients with T3N0 breast cancer treated from 1974 to 1994 with MRM who received no radiation and of whom, only 9% received adjuvant systemic therapy. Isolated LRF as first event was reported in 12 patients (12%); six of these patients experienced chest wall recurrence, and six experienced regional LN failure. The authors concluded that the risk of LRF in T3N0 is low and does not warrant the routine use of PMRT. In a combined analysis from the Massachusetts General Hospital, M.D. Anderson Cancer Center, and Yale University, Floyd et al,¹⁴ with a median follow-up time of 85 months, found that the 5-year actuarial cumulative rates of LRF in 70 node-negative patients with tumors 5 cm was 7.6%; four of the five failures occurred in the chest wall, and one occurred in the axilla. Tumor size and menopausal status were not found to be significant prognostic factors of LRF, but in a multivariate analysis, lymphatic vessel invasion (LVI) was found to be an independent prognostic factor for LRF, disease-free survival, and overall survival (OS). Although the low LRF rate in that series is in agreement with what we found, the study by Floyd et al¹⁴ was a retrospective study, and the omission of PMRT for the patients in their series was determined by patient and physician biases that may have affected the selection of the cohort analyzed.

All the patients in our series received no PMRT, as required by the different protocols. One might argue that, between 1981 and 1998, physicians who had patients at particularly high risk for LRF when PMRT was not an option might have been disinclined to enroll them in these NSABP studies. This is an unlikely scenario because in the same period (1984 to 1994) 5,758 patients with MRM and positive LNs (ie, considered higher risk patients) were accrued to node-positive NSABP trials that also did not allow PMRT.¹⁵ Almost 50% of the latter group had four positive LNs, and 11% had larger than 5 cm tumors with positive LNs. Therefore, it is unlikely that only node-negative, low-risk patients for LRF were selected to enroll onto the node-negative NSABP trials included in this analysis.

Several randomized studies have suggested that PMRT reduces the risk of LRF by two thirds and potentially increases OS.^16-18 These trials have targeted mainly patients with positive LNs. However, the randomized clinical trial reported by Overgaard et al,^16,17 in which patients were randomly assigned to cyclophosphamide, methotrexate, and fluorouracil chemotherapy versus cyclophosphamide, methotrexate, and fluorouracil plus PMRT, included 135 premenopausal¹⁶ and 132 postmenopausal¹⁷ patients with T3N0 tumors. The results in that group showed that PMRT decreased the LRF rate from 17% to 3% in premenopausal patients and from 23% to 6% in postmenopausal patients.^16,17 In addition, PMRT significantly increased the OS rate from 70% to 82% in premenopausal patients¹⁶ but did not significant increase OS in postmenopausal patients. However, in those studies, axillary LN dissection was considered suboptimal because an average of only seven LNs were removed^16,17 compared with 15 to 17 LNs removed in other studies.^15,19-21 Thus, it is possible that some of the T3N0 patients in the Overgaard et al^16,17 series may have been found to be node positive if additional axillary LNs had been removed at surgery. In our series, patients who had had one to five axillary LNs removed had a 16.7% isolated LRF rate, in contrast to 7.3% in patients who had had 10 or more LNs removed. Although the difference was not statistically significant because of the small number of patients who had one to five LNs removed (12 patients), the trend suggests that adequate LN dissection may be able to identify T3N0 patients with a lower risk for LRF.

As discussed earlier, the rate of LRF in T3N0 patients randomly assigned to the nonradiation arm in the Overgaard et al^16,17 trials was higher (17% to 23%) than the rate observed in our series (7.1%) or in other similar series (Floyd et al,¹⁴ 7.6%; and Mignano et al,¹³ 12%). This discrepancy between the randomized trials^16,17,22 and other series^15,19-21 in the LRF rate in patients who did not receive PMRT was also found in patients with one to three and four positive axillary LNs.¹⁵ Thus, the applicability of the findings from the randomized trials to current practice about the routine use of PMRT in patients with tumors larger than 5 cm and negative axillary nodes (by an adequate axillary dissection) who are treated with systemic therapy has been questioned.

As mentioned earlier, the univariate and multivariate analyses in our study did not show any significant prognostic factors for LRF or LRF ± DF. Although an adequate number of removed axillary LNs and the use of systemic treatment were found to be associated with better locoregional control, these associations were not statistically significant. This could be because the number of patients and, more importantly, the number of events were relatively small in our study. It is also possible that some potentially prognostic factors were not studied because of the lack of information in our database. These factors include LVI,^14,21,23,24 tumor grade,^21,23 human epidermal growth factor receptor 2 expression,^25,26 close margins,²⁴ p53 expression,²⁷ and presence of extensive intraductal component.²⁸ Floyd et al¹⁴ found that LVI was an independent prognostic factor for LRF. Nevertheless, tumor size, as long as the LNs were negative, was not found to be an independent prognostic factor for LRF in either of our series or the study by Floyd et al.¹⁴ In a recent retrospective analysis of 877 patients with T1-3 node-negative tumors treated at Massachusetts General Hospital with mastectomy without adjuvant PMRT, Jagsi et al²⁹ suggested that patients with multiple risk factors, including close margins, T2 or larger tumors, premenopausal status, and LVI, are at higher risk for LRF. However, only 25 patients (0.55%) had tumors larger than 5 cm.

Large breast tumors that present without the involvement of regional LNs may be a distinct clinical and biologic entity. It is possible that the inability of these tumors to spread to regional nodes despite their ability to grow to large size may indicate a more indolent biologic nature. This clinical presentation is clearly in contrast to the one in which small tumors have already spread to regional LNs and/or distant sites at the time of clinical presentation. The study of biologic differences and gene fingerprinting³⁰ between these extremes of tumor presentation may help in the understanding of the nature of the invasive and metastatic potential of breast tumors and in the identification of patients who would benefit from PMRT.

The most common PMRT approach used by radiation oncologists and in the cooperative group studies includes the area of the chest wall and regional LNs.^16,17,22 The risk of radiation pneumonitis increases with the number of radiation fields used as well as with the use of chemotherapy.^31,32 Furthermore, the risk for arm lymphedema increases when radiotherapy includes the regional lymph node.^33,34 All these facts raise the question of the need for regional radiation should radiation be used in this group of patients. Because the chest wall was by far the most common site of failure in this study (86%) as well as in the study by Floyd et al,¹⁴ it may be reasonable to consider treating the chest wall only, without radiating the regional LNs, in subsets of patients thought to be at higher risk, thereby minimizing the adverse effects of PMRT.

In our series, the 10-year cumulative incidence for LRF ± DF in patients who did not receive systemic treatment was 16.3% (13 of 80 patients) compared with 7.5% (eight of 107 patients), 7.7% (five of 66 patients), and 8.6% (five of 60 patients) in patients who received systemic adjuvant chemotherapy, adjuvant tamoxifen, or both, respectively (Table 3). However, the number of events was small, and these differences were not statistically significant. Most patients with 5-cm N0 tumors would now receive systemic treatment.⁸ Therefore, with systemic therapy, the overall LRF ± DF rate without PMRT in our study would be in the range of 6% to 7.7%, and the isolated LRF as first event rate would be in the range of 4.6% to 5.6% (Table 3). This rate is low enough that the benefit from routine PMRT might not outweigh its potential adverse effects. Furthermore, it is possible that a majority of this population might be treated with neoadjuvant chemotherapy because there would be a better chance for them under that circumstance to undergo conservative surgery.³⁵ To identify these low-risk patients, it might be reasonable for them to undergo up-front sentinel-node surgery; if the node is negative, the patient might not require PMRT or regional radiation if conservative approaches are used. A recent meta-analysis³⁶ suggested that an absolute reduction in LRF rate of approximately 20% is needed to improve survival by approximately 5%. Thus, it is unlikely that PMRT in this population will yield a significant improvement in survival.

In conclusion, the locoregional recurrence rate in this small population of node-negative patients with large tumors is lower than what radiation oncologists have perceived.³ We found no statistically significant risk factors for locoregional recurrence in this study. These data should be interpreted with caution because of the small number of patients and events and because LVI, grade, and margins were not among the factors that were included in our database, but the data suggest that pathologic tumor size alone, in the absence of positive LNs, should not be a basis for PMRT.

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
Although all authors completed the disclosure declaration, the following author or immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Authors Employment Leadership Consultant Stock Honoraria Research Funds Testimony Other Eleftherios P. Mamounas AstraZeneca (A) AstraZeneca (A)

Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C) $100,000 (N/R) Not Required

	Author Contributions

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 

Conception and design: Alphonse G. Taghian, Eleftherios P. Mamounas, Melvin Deutsch, Joseph P. Costantino, Norman Wolmark Administrative support: Joseph P. Costantino, Norman Wolmark Collection and assembly of data: Joseph P. Costantino Data analysis and interpretation: Alphonse G. Taghian, Jong-Hyeon Jeong, Eleftherios P. Mamounas, David S. Parda, Joseph P. Costantino Manuscript writing: Alphonse G. Taghian, Eleftherios P. Mamounas, David S. Parda, Melvin Deutsch, Joseph P. Costantino Final approval of manuscript: Alphonse G. Taghian, Jong-Hyeon Jeong, Eleftherios P. Mamounas, David S. Parda, Melvin Deutsch, Joseph P. Costantino, Norman Wolmark

 

	ACKNOWLEDGMENTS

 
We thank Barbara C. Good, PhD, and Wendy L. Rea for editorial assistance.

	NOTES

 
Supported by Public Health Service Grants No. U10CA-12027, U10CA-37377, U10CA-69974, and U10CA-69651 from the National Cancer Institute, Department of Health and Human Services.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
1. Helinto M, Blomqvist C, Heikkila P, et al: Post-mastectomy radiotherapy in pT3N0M0 breast cancer: Is it needed? Radiother Oncol 52: 213-217, 1999[CrossRef][Medline]

2. Recht A, Edge SB, Solin LJ, et al: Postmastectomy radiotherapy: Clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 19: 1539-1569, 2001[Abstract/Free Full Text]

3. Ceilley E, Jagsi R, Goldberg S, et al: Radiotherapy for invasive breast cancer in North America and Europe: Results of a survey. Int J Radiat Oncol Biol Phys 61: 365-373, 2005[CrossRef][Medline]

4. Fisher B, Redmond C, Dimitrov NV, et al: A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors. N Engl J Med 320: 473-478, 1989[Abstract]

5. Fisher B, Dignam J, Bryant J, et al: Five versus more than five years of tamoxifen therapy for breast cancer patients with negative lymph nodes and estrogen receptor-positive tumors. J Natl Cancer Inst 88: 1529-1542, 1996[Abstract/Free Full Text]

6. Fisher B, Costantino J, Redmond C, et al: A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N Engl J Med 320: 479-484, 1989[Abstract]

7. Fisher B, Dignam J, Mamounas E, et al: Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: Eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil. J Clin Oncol 14: 1982-1992, 1996[Abstract/Free Full Text]

8. Fisher B, Dignam J, Wolmark N, et al: Tamoxifen and chemotherapy for lymph node-negative, estrogen receptor-positive breast cancer. J Natl Cancer Inst 89: 1673-1682, 1997[Abstract/Free Full Text]

9. Fisher B, Anderson S, Tan-Chiu E, et al: Tamoxifen and chemotherapy for axillary node negative, estrogen receptor-negative breast cancer: Findings from the National Surgical Breast and Bowel Project B-23. J Clin Oncol 19: 931-942, 2001[Abstract/Free Full Text]

10. Kalbfleisch J, Prentice RL: The Statistical Analysis of Failure Time Data. New York, NY, John Wiley and Sons, 1980

11. Gray R: A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 16: 1141-1154, 1988

12. Cox D: Regression models and life-tables. J R Stat Soc B 34: 187-220, 1972

13. Mignano J, Gage I, Piantatosi S, et al: Local recurrence after mastectomy in patients with T3N0 breast carcinoma treated without postoperative irradiation. Breast Cancer Res Treat 41: 255, 1996 (abstr 230)

14. Floyd S, Buchholz TA, Haffty B, et al: Low local recurrence rate without post-mastectomy radiation in node negative breast cancer patients with tumors 5 cm and larger. Int J Radiat Oncol Biol Phys (in press)

15. Taghian A, Jeong J-H, Mamounas E, et al: Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: Results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials. J Clin Oncol 22: 4247-4254, 2004[Abstract/Free Full Text]

16. Overgaard M, Hansen PS, Overgaard J, et al: Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 337: 949-955, 1997[Abstract/Free Full Text]

17. Overgaard M, Jensen MB, Overgaard J, et al: Postoperative radiotherapy in high-risk postmenopausal breast cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomized trial. Lancet 353: 1641-1648, 1999[CrossRef][Medline]

18. Ragaz J, Jackson SM, Le N, et al: Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med 337: 956-962, 1997[Abstract/Free Full Text]

19. Recht A, Gray R, Davidson N, et al: Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamoxifen without irradiation: Experience of the Eastern Cooperative Oncology Group. J Clin Oncol 17: 1689-1700, 1999[Abstract/Free Full Text]

20. Katz A, Strom E, Buchholz T, et al: Locoregional recurrence patterns after mastectomy and doxorubicin-based chemotherapy: Implications for postoperative irradiation. J Clin Oncol 18: 2817-2827, 2000[Abstract/Free Full Text]

21. Wallgren A, Bonetti M, Gelber RD, et al: Risk factors for locoregional recurrence among breast cancer patients: Results from International Breast Cancer Study Group trials I through VII. J Clin Oncol 21: 1205-1213, 2003[Abstract/Free Full Text]

22. Ragaz J, Olivotto IA, Spinelli JJ, et al: Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst 97: 116-126, 2005[Abstract/Free Full Text]

23. Pisansky T, Ingle JN, Schaid DJ, et al: Patterns of tumor relapse following mastectomy and adjuvant systemic therapy in patients with axillary lymph node-positive breast cancer. Cancer 72: 1247-1260, 1993[CrossRef][Medline]

24. Katz A, Strom EA, Buchholz TA, et al: The influence of pathologic tumor characteristics on locoregional recurrence rates following mastectomy. Int J Radiat Oncol Biol Phys 50: 735-742, 2001[CrossRef][Medline]

25. Paik S, Bryant J, Park C, et al: ErbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. J Natl Cancer Inst 90: 1361-1370, 1998[Abstract/Free Full Text]

26. Paik S, Bryant J, Tan-Chiu E, et al: HER2 and choice of adjuvant chemotherapy for invasive breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-15. J Natl Cancer Inst 92: 1991-1998, 2000[Abstract/Free Full Text]

27. Zellars R, Clark, GM, Allred, DC, et al: Prognostic value of p53 for local failure in mastectomy treated breast cancer patients. Proc Am Soc Clin Oncol 17: 104a, 1998 (abstr 401)

28. Voogd A, Nielsen M, Peterse JL, et al: Differences in risk factors for local and distant recurrence after breast-conserving therapy or mastectomy for stage I and II breast cancer: Pooled results of two large European randomized trials. J Clin Oncol 19: 1688-1697, 2001[Abstract/Free Full Text]

29. Jagsi R, Raad RA, Goldberg S, et al: Locoregional recurrence rates and prognostic factors for failure in node-negative patients treated with mastectomy: Implications for postmastectomy radiation. Int J Radiat Oncol Biol Phys 62: 1035-1039, 2005[CrossRef][Medline]

30. Paik S, Shak S, Tang G, et al: A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351: 2817-2826, 2004[Abstract/Free Full Text]

31. Lingos T, Recht A, Vicini F, et al: Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys 21: 355-360, 1991[Medline]

32. Taghian A, Assaad S, Niemierko A, et al: Risk of pneumonitis in breast cancer patients treated with radiation therapy and combination chemotherapy with paclitaxel. J Natl Cancer Inst 93: 1806-1811, 2001[Abstract/Free Full Text]

33. Coen JJ, Taghian AG, Kachnic LA, et al: Risk of lymphedema after regional nodal irradiation with breast conservation therapy. Int J Radiat Oncol Biol Phys 55: 1209-1215, 2003[CrossRef][Medline]

34. Højris I, Anderson J, Overgaard M, et al: Late treatment related morbidity in breast cancer patients randomized to postmastectomy radiotherapy and systemic treatment versus systemic treatment alone. Eur J Cancer 35: S206, 1999 (suppl 4, abstr 803)

35. Fisher B, Bryant J, Wolmark N, et al: Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 16: 2672-2685, 1998[Abstract]

36. Early Breast Cancer Trialists' Collaborative Group: Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: An overview of the randomised trials. Lancet 366: 2087-2106, 2005[Medline]

Submitted April 5, 2006; accepted June 16, 2006.

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Taghian, A. G. Articles by Wolmark, N. Search for Related Content PubMed PubMed Citation Articles by Taghian, A. G. Articles by Wolmark, N.