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Originally published as JCO Early Release 10.1200/JCO.2005.12.044 on November 15 2004 © 2005 American Society of Clinical Oncology.
Effect of Addition of Adjuvant Paclitaxel on Radiotherapy Delivery and Locoregional Control of Node-Positive Breast Cancer: Cancer and Leukemia Group B 9344From the University of North Carolina, Chapel Hill; Cancer and Leukemia Group B Statistical Center, Durham, NC; Quality Assurance Review Center, Providence, RI; Medical University of South Carolina, Charleston, SC; State University of New York Upstate Medical University, Syracuse; Memorial Sloan-Kettering Cancer Center, New York, NY; and University of California San Francisco, San Francisco, CA Address reprint requests to Carolyn I. Sartor, MD, Dept of Radiation Oncology, University of North Carolina School of Medicine, CB7512, Chapel Hill, NC 27599; e-mail: csartor{at}med.unc.edu
PURPOSE: We compared radiotherapy (RT) delivery and locoregional control in patients with node-positive breast cancer randomly assigned on Cancer and Leukemia Group B 9344 to receive adjuvant doxorubicin/cyclophosphamide (AC) with patients assigned to receive AC followed by paclitaxel (AC+T). METHODS: Eligible patients were randomly assigned to receive adjuvant AC versus AC+T chemotherapy. RT was required if breast-conserving surgery was performed but was elective after mastectomy. Information about RT delivery was retrospectively collected. Cumulative incidence of locoregional recurrence (LRR), use of elective RT, and RT delivery were compared between treatment arms. RESULTS: For patients treated with breast-conserving surgery and RT, the 5-year cumulative incidence of isolated LRR was 9.7% in the AC arm and 3.7% in the AC+T arm (P = .04) and of LRR as any component of failure was 12.9% versus 6.1%, respectively (P = .04). Although LRR rates in patients who did not receive postmastectomy RT were lower in the AC+T arm, the difference was not statistically significant. Despite the lack of protocol guidelines, RT use did not differ between arms, nor did RT dose, treatment interruption, or completion. CONCLUSION: Despite the delay to RT during additional chemotherapy, adjuvant AC+T afforded better local control than AC alone in patients treated with breast-conserving therapy. Addition of paclitaxel did not adversely affect delivery or ability to tolerate RT, as indicated by similar rates of completion of timely, full-dose RT between arms.
Advances in adjuvant chemotherapy for breast cancer include the sequential delivery of non-cross-resistant agents. Intergroup 0148 (Cancer and Leukemia Group B [CALGB] 9344) was a randomized trial that tested, in a 3 x 2 design, the benefit of doxorubicin dose escalation and of sequential addition of four cycles of paclitaxel to four cycles of adjuvant doxorubicin/cyclophosphamide (AC) in patients with early-stage breast cancer metastatic to axillary lymph nodes. AC plus paclitaxel (AC+T) resulted in superior overall and disease-free survival compared with AC.1 Despite the improvement of systemic disease control with additional chemotherapy, delay to adjuvant radiotherapy (RT) could adversely affect local control.2–6 However, the superior efficacy of AC+T could translate into improved local control. To determine the effect on local control of the additional four cycles of paclitaxel, we evaluated locoregional recurrence (LRR) in patients treated with AC versus AC+T. This was, in fact, one of the primary objectives of Intergroup 0148. Intergroup 0148 required adjuvant RT after breast-conserving surgery (BCS), but adjuvant postmastectomy RT was discretionary. The use of postmastectomy RT for patients at intermediate risk of LRR is highly controversial.7–11 Although postmastectomy RT reduces the risk of LRR by two thirds, translating into improved breast cancer-specific mortality, the benefit is at least partially offset by radiation-induced toxicity.12–14 Modern RT techniques likely reduce the risk of radiation-induced cardiac sequelae, resulting in more favorable risk-to-benefit ratio.15,16 Nonetheless, the magnitude of the benefit of postmastectomy RT depends also on the risk of LRR without RT. Rates of LRR in patients treated with mastectomy and adjuvant anthracycline- or non-anthracycline-based chemotherapy without adjuvant RT are available to estimate the benefit of postmastectomy RT.17 However, if more efficacious chemotherapy regimens significantly reduce LRR, some patients who traditionally were estimated to be at intermediate risk of LRR may actually be at lower risk. Thus we wished to determine LRR rates in patients treated with AC versus AC+T who were not treated with postmastectomy RT. Taxanes are potent radiosensitizers.18,19 Although RT was delivered after completion of chemotherapy, a potential concern is that paclitaxel may have increased RT-related toxicity or impaired ability to deliver timely, full-dose RT. Therefore, we also wished to determine whether addition of paclitaxel adversely affected RT delivery. Because Intergroup 0148 was designed to address chemotherapy-related questions, RT-related data were not prospectively collected. Thus data regarding whether patients were treated with postmastectomy RT and compliance with protocol-stipulated breast RT were unknown. To address the issues of effect of paclitaxel on LRR and RT delivery, we retrospectively collected RT treatment information for the patients enrolled onto Intergroup 0148 through CALGB-participating institutions to determine the following: LRR rates in patients treated with RT with or without paclitaxel, LRR rates in patients treated with mastectomy without postmastectomy RT with or without paclitaxel, and RT delivery in patients treated with RT with or without paclitaxel.
Patient and Treatment Characteristics Between 1994 and 1997, 3,170 patients with node-positive, nonmetastatic breast cancer were enrolled, after signing informed consent, onto Intergroup 0148/CALGB 9344, which was performed in accordance with an assurance filed with and approved by the United States Department of Health and Human Services.1 Eligible patients underwent complete tumor resection by mastectomy or lumpectomy and axillary node dissection with negative surgical margins. Patients were randomly assigned at the CALGB Statistical Center to receive one of three doses of doxorubicin (60, 75, or 90 mg/m2) plus 600 mg/m2 of cyclophosphamide for four 21-day cycles followed by a second randomization to receive or not receive four 21-day cycles of paclitaxel 175 mg/m2. The vast majority of patients whose tumors expressed the estrogen receptor or progesterone receptor received adjuvant tamoxifen (94%), as did 21% of patients whose tumors were receptor-negative. Patients treated with BCS were required by protocol to receive adjuvant RT after completion of chemotherapy, but no other RT treatment guidelines were given. RT treatment ports were not protocol-specified; some patients received RT targeting both breast and regional lymph nodes, whereas others received breast RT only. The use of postmastectomy RT was neither required nor forbidden in Intergroup 0148. Rather, postmastectomy RT was elective, left to the discretion of the treating physician and patient. If delivered, postmastectomy RT was given after completion of adjuvant chemotherapy.
Toxicity Monitoring and Follow-Up
RT Data Retrieval
Statistical Analysis
LRR After Breast-Conserving Therapy With and Without Paclitaxel The demographics of CALGB-enrolled patients treated with BCS and RT are listed in Table 1. Among all patients treated with BCS who had information on whether they received RT, 125 (93%) of the 135 patients randomly assigned to receive AC were treated per protocol with RT as compared with 144 (87%) of the 166 patients randomly assigned to receive AC+T. Compliance with protocol-stipulated RT did not differ by arm (P = .13). Recurrence patterns among the patients receiving RT are shown in Table 2. The cumulative incidence of LRR as first failure (isolated LRR) or as any component of failure among the patients receiving RT is shown in Figure 2. Despite the delay to RT during additional chemotherapy, patients who received AC+T had a lower rate of isolated LRR (P = .04) or LRR as any component of failure (P = .04). The 5-year incidence of isolated LRR for AC was 9.7% (SE = 2.7) versus 3.7% (SE = 1.9) for AC+T; the 5-year incidence of LRR as any component of failure was 12.9% (SE = 3.0) versus 6.1% (SE = 2.1), respectively. Interestingly, if patients who did not receive RT (protocol violation) were included, there was no statistically significant difference in local recurrence between arms. We found no association between age, tumor size, number of involved nodes, tamoxifen use, or menopausal status and likelihood of receiving RT per protocol.
The data collected on local recurrence did not distinguish ipsilateral breast recurrence from regional nodal recurrence; occurrence of both or either was coded as LRR. Because LRR rates could differ depending on volume of radiation, and because nodal recurrence could be less likely in patients whose regional lymph nodes were irradiated, we compared LRR between arms in the subset of 96 BCS patients treated homogeneously with breast and nodal RT. The probability of BCS patients receiving nodal RT did not differ between the AC and AC+T treatment arms (45 [47%] of 95 patients v 51 [49%] of 104 patients, respectively). An effect of paclitaxel on LRR was still seen (Figs 3A and 3B).
LRR After Postmastectomy RT With or Without Paclitaxel Table 3 shows disease and patient characteristics by arm of patients who were treated with mastectomy. Despite the lack of protocol guidelines, use of elective postmastectomy RT did not differ between arms. Recurrence patterns for 98 AC and 87 AC+T patients treated with postmastectomy RT are shown in Table 4. The incidence of LRR in these patients was low in both the AC and AC+T treatment arms (Figs 4A and 4B). The 5-year incidence of isolated LRR for patients treated with AC was 4.3% (SE = 2.1) versus 3.5% (SE = 2.0) for patients treated with AC+T. The 5-year incidences of LRR as any component of failure were identical to these. Thus delay to postmastectomy RT while receiving additional chemotherapy did not impair efficacy of RT.
LRR With or Without Paclitaxel in Patients Who Did Not Receive Postmastectomy RT Recurrence patterns for the 253 AC and 245 AC+T patients who did not receive elective postmastectomy RT are given in Table 5. The cumulative incidence of LRR was not significantly different between arms (Figs 5A and 4B). The 5-year incidence of isolated LRR for patients treated with AC was 10.8% (SE = 2.0) versus 8.8% (SE = 1.9) for patients treated with AC+T. The 5-year incidence of LRR as any component of failure for patients treated with AC was 14.9% (SE = 2.3) versus 11.7% (SE = 2.1) for patients treated with AC+T. Because estimates of the risk of LRR in patients treated with or without paclitaxel are particularly relevant for evaluating the risk-to-benefit ratio of controversial postmastectomy RT in patients at intermediate risk for recurrence, we evaluated rates of LRR in postmastectomy patients with one to three involved lymph nodes who did not receive RT. The cumulative incidence of isolated LRR in patients treated with AC versus AC+T was 9.3% (SE = 2.6) versus 5.2% (SE = 2.1), respectively (P = .17). As shown in Table 6, among the analogous group of patients with four or more nodes, the cumulative incidence was identical for AC as for AC+T (12.4%), although the interaction between treatment arm and number of nodes was not significant (P = .36).
Effect of Paclitaxel on RT Delivery Taxanes are potent radiosensitizers. Thus although the sequential addition of paclitaxel improved LRR, paclitaxel could also have increased RT-related toxicity. Acute chemotherapy-related toxicity and long-term cardiac toxicity were captured on Intergroup 0148, but RT-related toxicity was not prospectively monitored. To determine whether 340 mastectomy and BCS patients tolerated RT as well after AC+T as AC, we examined whether patients completed prescribed therapy, RT treatment interruption, time required to complete RT, and total dose. There was no difference in mean total RT dose or duration, percentage of patients who completed RT, or incidence of treatment interruptions between arms (Table 7). There was also no difference in the time from completion of chemotherapy to initiation of RT, suggesting that there was no excess toxicity in the AC+T arm that consistently resulted in delay to initiation of RT after completion of chemotherapy. Thus completion of timely, full-dose RT was not adversely affected by the addition of paclitaxel, suggesting that there was no clinically significant increase in acute RT-related toxicity.
This randomized comparison of AC versus AC+T demonstrates that sequential addition of paclitaxel improves locoregional control in patients treated with BCS and RT despite delay to RT. Although the effect of chemotherapy on reducing ipsilateral breast tumor recurrence in patients treated with BCS is well-established, several retrospective studies and one prospective study have demonstrated decreased local control in patients for whom RT was delayed until the completion of chemotherapy, suggesting that delay to RT while delivering longer chemotherapy regimens may impair RT efficacy.2–6,22–24 However, other studies have not shown a detrimental effect on local control of delaying RT during adjuvant chemotherapy.25–28 The improved local control on the AC+T arm despite delay to RT may be due to the superior efficacy of paclitaxel, longer duration of chemotherapy, radiosensitizing effects of paclitaxel, or any combination of these or other factors. Because we were evaluating the effect of paclitaxel versus delay to RT in patients treated with breast-conserving therapy, our primary analysis was restricted to patients who received RT as required per protocol. However, when we analyzed the data by intention to treat, we found no improvement in local control with the addition of paclitaxel if we included the patients who did not receive RT. One possible explanation for an effect only in patients receiving RT is that the addition of paclitaxel has an insubstantial effect in the setting of higher risk of LRR without RT. Another is that the paclitaxel reduces LRR through a radiosensitization effect. Either of these explanations is purely speculative, and we will investigate the possible dependence of local control benefit of paclitaxel on RT when additional follow-up allows for analysis of more events. It is possible that local control could be further improved by earlier delivery of RT, as occurs with dose-dense scheduling of adjuvant chemotherapy. Analysis of CALGB 9741 may help to distinguish an effect of paclitaxel versus duration of chemotherapy and delay to RT on local control by comparing local control rates in patients who received RT after dose-dense AC+T versus conventional AC+T. Although it is possible that local control could be further improved by earlier delivery of RT, such as between the AC and paclitaxel phases, the potential improvement in local control should be balanced against the potential for decreased systemic efficacy with delay of systemic therapy.6 One of the more controversial subjects in breast cancer treatment is the use of elective postmastectomy RT. Although results of recent trials and meta-analyses indicate that postmastectomy RT likely improves survival in select patients, the magnitude of the benefit depends on the risk of LRR as the first site of recurrence.29–33 Five-year local recurrence rates in large, randomized series of mastectomy and systemic therapy range from 2% to 11% in patients treated with adjuvant RT versus 5% to 25% in patients treated without adjuvant RT.34–37 Although postmastectomy RT delivery was not controlled in this trial, our retrospective review of RT delivery provides useful information regarding LRR rates in patients treated with the addition of paclitaxel. The incidence of isolated LRR in patients treated with mastectomy without adjuvant RT in our trial was 11% at 5 years for those treated with AC and 9% for those treated with AC+T. The risk of LRR was much less (approximately 4%) in those treated with adjuvant RT. In the subset of patients for whom postmastectomy RT is most controversial (ie, intermediate-risk patients with one to three involved lymph nodes), we found that the risk of isolated local recurrence in patients randomly assigned to receive AC was higher than those who received AC+T after mastectomy without RT (9.3% v 5.2%, respectively). This difference was not statistically significant. Our study, with only 18 events in the relevant subset, did not have the power to detect a true difference of this magnitude. It may be possible to discern an effect of paclitaxel, if it indeed exists, on LRR in patients with one to three involved lymph nodes treated with mastectomy without adjuvant RT if our data are combined with the similarly treated cohort from National Surgical Breast and Bowel Project (NSABP) Trial B-28. It should be noted that our follow-up time is relatively short and that longer follow-up with more local events will also increase the power to see a difference. The issue of local effect of AC+T is particularly relevant, because the randomized trial designed to specifically determine the benefit of postmastectomy RT in intermediate-risk patients treated with adjuvant anthracycline-containing chemotherapeutic regimens has been prematurely terminated because of low accrual. If chemotherapeutic advances truly reduce the risk of LRR after mastectomy, then the role of postmastectomy RT may be diminished. However, we emphasize the limitations inherent in our study. Postmastectomy RT delivery was not controlled, allowing potential for bias or imbalance between groups. The data in the postmastectomy subset should be interpreted with the caution appropriate to retrospective reviews. One caveat in interpretation of the potential locoregional benefit of AC+T is that the risk of LRR after mastectomy in the AC arm was higher in our study than has been reported in some others. For instance, NSABP B-06 reported an LRR rate of 6% at 8 years for node-positive disease treated with breast-conserving RT and adjuvant chemotherapy.38 Although eligibility for NSABP B-06 was limited to a tumor size of 4 cm, a similar incidence of local recurrence was identified in the adjuvant arm of NSABP B-18, which allowed larger tumors.39 One explanation for the higher rates of local recurrence is that our definition of local recurrence included recurrence in the treated breast or in the regional lymph nodes, whereas the NSABP studies discussed above specifically define in-breast recurrence. Furthermore, actuarial estimates of LRR rates in different studies may be difficult to reconcile because of competing risks of failure in other sites.40 A review of failure patterns in patients treated with breast-conserving therapy at the Joint Center for Radiation Therapy demonstrated an 8-year crude local failure rate of 34% in patients with involved lymph nodes who received radiation treatment to the breast without regional nodal irradiation.41 One third of the recurrences were regional recurrences and would thus not have been indicated in NSABP's rates of ipsilateral breast recurrence. Because patients treated with breast-conserving therapy on our trial were also likely to be treated with breast-only RT, recurrence in the unirradiated regional lymph nodes may account for higher rates of LRR in this study compared with trials that report rates of recurrence only in the irradiated breast. LRR rates in patients who received elective nodal irradiation were still relatively high in the AC arm (13% at 5 years), but these patients also had a higher burden of nodal involvement and thus were likely at higher risk of LRR than many patients treated on early-stage breast-conserving therapy trials. Margin status clearly influences the risk of local recurrence; although eligibility was restricted in our study to patients whose tumors were excised with negative margins, we do not know how close the margins were.9,11,12,42 Patients treated on this trial were less likely to receive postmastectomy RT than those treated today. It is therefore encouraging to see that the delay to RT because of sequential delivery of AC+T did not adversely affect LRR. In patients who received postmastectomy RT, recurrence rates were very low, obscuring any potential effect of paclitaxel on local control in this subset. With the increased use of AC+T and postmastectomy RT, we might hope to see lower recurrence rates than previously. We discerned no effect of the addition of paclitaxel on ability to complete timely, full-dose RT, suggesting that paclitaxel did not significantly increase acute toxicity during RT. However, it should be noted that we were unable to evaluate with confidence whether addition of paclitaxel increased RT-related toxicity, because RT-specific toxicity, acute or chronic, was not prospectively captured. Ongoing CALGB trials are prospectively evaluating acute and chronic RT-related toxicity. It is particularly important to evaluate the possibility of increased toxicity as more patients receive paclitaxel as a component of their adjuvant regimen, particularly as delivery of chemotherapy is intensified. At least two studies have reported increased rates of radiation pneumonitis with concurrent and sequential taxane-RT regimens.43,44 Although some studies indicate no significant increase in acute toxicity with concurrent taxane-RT regiments, the fact that sequential addition of paclitaxel demonstrated no adverse effect on RT efficacy may temper enthusiasm for concurrent therapy in all but high-risk patients.45,46
The following institutions participated in the study: CALGB Statistical Office, Durham, NC: Stephen George, PhD, supported by grant No. CA33601; Baptist Cancer Institute Community Clinical Oncology Program (CCOP), Memphis, TN: Lee S. Schwartzberg, MD, supported by grant No. CA71323; Christiana Care Health Services, Inc. CCOP, Wilmington, DE: Irving M. Berkowitz, DO, supported by grant No. CA45418; Community Hospital-Syracuse CCOP, Syracuse, NY: Jeffrey Kirshner, MD, supported by grant No. CA45389; Dana-Farber Cancer Institute, Boston, MA: George P. Canellos, MD, supported by grant No. CA32291; Dartmouth Medical School-Norris Cotton Cancer Center, Lebanon, NH: L. Herbert Maurer, MD, supported by grant No. CA04326; Duke University Medical Center, Durham, NC: Jeffrey Crawford, MD, supported by grant No. CA47577; Eastern Cooperative Oncology Group, Philadelphia, PA: Robert L. Comis, MD, Chair; Green Mountain Oncology Group CCOP, Bennington, VT: H. James Wallace Jr, MD, supported by grant No. CA35091; Kaiser Permanente CCOP, San Diego, CA: Jonathan A. Polikoff, MD, supported by grant No. CA45374; Long Island Jewish Medical Center, Lake Success, NY: Marc Citron, MD, supported by grant No. CA11028; Massachusetts General Hospital, Boston, MA: Michael L. Grossbard, MD, supported by grant No. CA12449; Mount Sinai Medical Center CCOP-Miami, Miami Beach, FL: Enrique Davila, MD, supported by grant No. CA45564; Mount Sinai School of Medicine, New York, NY: James F. Holland, MD, supported by grant No. CA04457; North Central Cancer Treatment Group, Rochester, MN: Michael J. O'Connell, MD, Chair, supported by grant No. CA25224; North Shore University Hospital CCOP, Manhasset, NY: Vincent Vinciguerra, MD, supported by grant No. CA35279; North Shore University Hospital, Manhasset, NY: Daniel R. Budman, MD, supported by grant No. CA35279; Rhode Island Hospital, Providence, RI: Louis A. Leone, MD, supported by grant No. CA08025; Roswell Park Cancer Institute, Buffalo, NY: Ellis Levine, MD, supported by grant No. CA02599; South New Jersey CCOP, Camden, NJ: Jack Goldberg, MD, supported by grant No. CA54697; Southeast Cancer Control Consortium Inc CCOP, Goldsboro, NC: James N. Atkins, MD, supported by grant No. CA45808; Southern Nevada Cancer Research Foundation CCOP, Las Vegas, NV: John Ellerton, MD, supported by grant No. CA35421; Southwest Oncology Group, San Antonio, TX: Charles Coltman, MD, Chair; St Michael's Medical Center Tri-County CCOP, Paterson, NJ: Arnold D. Rubin, MD, supported by grant No. CA60247; State University of New York Health Science Center at Syracuse, Syracuse, NY: Stephen L. Graziano, MD, supported by grant No. CA21060; University of Alabama at Birmingham, Birmingham, AL: Robert Diasio, MD, supported by grant No. CA47545; University of California San Diego, San Diego, CA: Stephen L. Seagren, MD, supported by grant No. CA11789; University of California San Francisco, San Francisco, CA: Alan P. Venook, MD, supported by grant No. CA60138; University of Chicago Medical Center, Chicago, IL: Nicholas J. Vogelzang, MD, supported by grant No. CA41287; University of Illinois at Chicago, Chicago, IL: Jeffrey A. Sosman, MD, supported by grant No. CA74811; University of Iowa Hospitals, Iowa City, IA: Gerald H. Clamon, MD, supported by grant No. CA47642; University of Maryland Cancer Center, Baltimore, MD: David Van Echo, MD, supported by grant No. CA31983; University of Massachusetts Medical Center, Worcester, MA: F. Marc Stewart, MD, supported by grant No. CA37135; University of Minnesota, Minneapolis, MN: Bruce A. Peterson, MD, supported by grant No. CA16450; University of Missouri/Ellis Fischel Cancer Center, Columbia, MO: Michael C. Perry, MD, supported by grant No. CA12046; University of Nebraska Medical Center, Omaha, NE: Anne Kessinger, MD, supported by grant No. CA77298; University of North Carolina at Chapel Hill, Chapel Hill, NC: Thomas C. Shea, MD, supported by grant No. CA47559; University of Tennessee Memphis, Memphis, TN: Harvey B. Niell, MD, supported by grant No. CA47555; Vermont Cancer Center, Burlington, VT: Hyman B. Muss, MD, supported by grant No. CA77406; Virginia Commonwealth University MB CCOP, Richmond, VA: John D. Roberts, MD, supported by grant No. CA52784; Wake Forest University School of Medicine, Winston-Salem, NC: David D. Hurd, MD, supported by grant No. CA03927; Walter Reed Army Medical Center, Washington, DC: John C. Byrd, MD, supported by grant No. CA26806; Washington University School of Medicine, St. Louis, MO: Nancy L. Bartlett, MD, supported by grant No. CA77440; and Weill Medical College of Cornell University, New York, NY: Ted P Szatrowski, MD, supported by grant No. CA07968.
The following authors or their immediate family members have 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. Consultant/Advisory Role: Andrew J. Turrisi, Aventis, AstraZeneca. Honoraria: Andrew J. Turrisi, Aventis; I. Craig Henderson, Bristol-Myers Squibb Co. Expert Testimony: Andrew J. Turrisi, Rovner, QACA.
Supported by grant Nos. CA47559, CA33601, CA29511, CA03927, CA21060, CA60138, and CA77651. The research for Cancer and Leukemia Group B 9344 was supported in part by grants from the National Cancer Institute (grant No. CA31946) to the Cancer and Leukemia Group B (Richard L. Schilsky, MD, Chair) and grant No. CA29511 to the Quality Assurance Review Center (T.J. FitzGerald, MD, Director). The contents of the manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003. Authors' disclosures of potential conflicts of interest are found at the end of this article.
1. Henderson IC, Berry DA, Demetri GD, et al: Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 21:976–983, 2003 2. Harris JR, Recht A: Sequencing adjuvant chemotherapy and radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys 26:183–185, 1993[Medline] 3. Hartsell WF, Recine DC, Griem KL, et al: Delaying the initiation of intact breast irradiation for patients with lymph node positive breast cancer increases the risk of local recurrence. Cancer 76:2497–2503, 1995[CrossRef][Medline] 4. Buchholz TA, Austin-Seymour MM, Moe RE, et al: Effect of delay in radiation in the combined modality treatment of breast cancer. Int J Radiat Oncol Biol Phys 26:23–35, 1993[Medline] 5. Ampil FL, Burton GV, Li BD, et al: Radiotherapy with and without chemotherapy after breast conservation surgery for early stage breast cancer: A review of timing. Eur J Gynaecol Oncol 20:254–257, 1999[Medline]
6. Recht A, Come SE, Henderson IC, et al: The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer. N Engl J Med 334:1356–1361, 1996 7. Recht A: The return (?) of postmastectomy radiotherapy. J Clin Oncol 13:2861–2864, 1995[Medline] 8. Recht A, Bartelink H, Fourquet A, et al: Postmastectomy radiotherapy: Questions for the twenty-first century. J Clin Oncol 16:2886–2889, 1998[Medline] 9. Harris JR, Halpin-Murphy P, McNeese M, et al: Consensus statement on postmastectomy radiation therapy. Int J Radiat Oncol Biol Phys 44:989–990, 1999[CrossRef][Medline] 10. Marks LB, Prosnitz LR: "One to three" or "four or more"? Selecting patients for postmastectomy radiation therapy. Cancer 79:668–670, 1997[CrossRef][Medline]
11. 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 12. 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[Abstract]
13. Early Breast Cancer Trialists' Collaborative Group: Effects of radiotherapy and surgery in early breast cancer: An overview of the randomized trials. N Engl J Med 333:1444–1455, 1995 14. Early Breast Cancer Trialists' Collaborative Group: Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomised trials. Lancet 355:1757–1770, 2000[CrossRef][Medline] 15. Kuske RR: Adjuvant chest wall and nodal irradiation: Maximize cure, minimize late cardiac toxicity. J Clin Oncol 16:2579–2582, 1998[Medline] 16. Pierce LJ, Lichter AS: Postmastectomy radiotherapy: More than locoregional control. J Clin Oncol 12:444–446, 1994[Medline]
17. Recht A, Gray R, Davidson NE, 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 18. Milas L, Milas MM, Mason KA: Combination of taxanes with radiation: Preclinical studies. Semin Radiat Oncol 9:12–26, 1999[Medline] 19. Choy H: Concurrent paclitaxel and radiation therapy in the treatment of solid tumors. Semin Radiat Oncol 9:1–3, 1999 20. Kalbfleisch J, Prentice R: The statistical analysis of failure time data. New York, NY, John Wiley and Sons, 1980 21. Fine J, Gray R: A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509
22. Fisher B, Dignam J, Mamounas EP, 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
23. Park CC, Mitsumori M, Nixon A, et al: Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: Influence of margin status and systemic therapy on local recurrence. J Clin Oncol 18:1668–1675, 2000
24. Buchholz TA, Tucker SL, Erwin J, et al: Impact of systemic treatment on local control for patients with lymph node-negative breast cancer treated with breast-conservation therapy. J Clin Oncol 19:2240–2246, 2001 25. Fisher B, Brown AM, Dimitrov NV, et al: Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: Results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 8:1483–1496, 1990[Abstract] 26. Wallgren A, Bernier J, Gelber RD, et al: Timing of radiotherapy and chemotherapy following breast-conserving surgery for patients with node-positive breast cancer: International Breast Cancer Study Group. Int J Radiat Oncol Biol Phys. 35:649–659, 1996[CrossRef][Medline] 27. Buzdar AU, Kau SW, Smith TL, et al: The order of administration of chemotherapy and radiation and its effect on the local control of operable breast cancer. Cancer 71:3680–3684, 1993[CrossRef][Medline] 28. Leonard CE, Wood ME, Zhen B, et al: Does administration of chemotherapy before radiotherapy in breast cancer patients treated with conservative surgery negatively impact local control? J Clin Oncol 13:2906–2915, 1995[Abstract]
29. 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 30. 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 randomised trial. Lancet 353:1641–1648, 1999[CrossRef][Medline]
31. 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
32. Whelan TJ, Julian J, Wright J, et al: Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. J Clin Oncol 18:1220–1229, 2000 33. Van de Steene J, Soete G, Storme G: Adjuvant radiotherapy for breast cancer significantly improves overall survival: The missing link. Radiother Oncol 55:263–272, 2000[CrossRef][Medline] 34. McArdle CS, Crawford D, Dykes EH, et al: Adjuvant radiotherapy and chemotherapy in breast cancer. Br J Surg 73:264–266, 1986[Medline] 35. Ahmann DL, O'Fallon JR, Scanlon PW, et al: A preliminary assessment of factors associated with recurrent disease in a surgical adjuvant clinical trial for patients with breast cancer with special emphasis on the aggressiveness of therapy. Am J Clin Oncol 5:371–381, 1982[Medline]
36. Griem KL, Henderson IC, Gelman R, et al: The 5-year results of a randomized trial of adjuvant radiation therapy after chemotherapy in breast cancer patients treated with mastectomy. J Clin Oncol 5:1546–1555, 1987
37. Fowble B, Gray R, Gilchrist K, et al: Identification of a subgroup of patients with breast cancer and histologically positive axillary nodes receiving adjuvant chemotherapy who may benefit from postoperative radiotherapy. J Clin Oncol 6:1107–1117, 1988 38. Fisher B, Redmond C, Poisson R, et al: Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 320:822–828, 1989[Abstract] 39. 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] 40. Gelman R, Gelber R, Henderson IC, et al: Improved methodology for analyzing local and distant recurrence. J Clin Oncol 8:548–555, 1990[Abstract] 41. Galper S, Recht A, Silver B, et al: Factors associated with regional nodal failure in patients with early stage breast cancer with 0-3 positive axillary nodes following tangential irradiation alone. Int J Radiat Oncol Biol Phys 45:1157–1166, 1999[CrossRef][Medline] 42. Cuzick J, Stewart H, Peto R, et al: Overview of randomized trials of postoperative adjuvant radiotherapy in breast cancer. Cancer Treat Rep 71:15–29, 1987[Medline]
43. Taghian AG, Assaad SI, 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 44. Hanna YM, Baglan KL, Stromberg JS, et al: Acute and subacute toxicity associated with concurrent adjuvant radiation therapy and paclitaxel in primary breast cancer therapy. Breast J 8:149–153, 2002[CrossRef][Medline] 45. Bellon JR, Lindsley KL, Ellis GK, et al: Concurrent radiation therapy and paclitaxel or docetaxel chemotherapy in high-risk breast cancer. Int J Radiat Oncol Biol Phys 48:393–397, 2000[CrossRef][Medline] 46. Formenti SC, Symmans WF, Volm M, et al: Concurrent paclitaxel and radiation therapy for breast cancer. Semin Radiat Oncol 9:34–42, 1999[Medline] Submitted December 9, 2003; accepted July 6, 2004.
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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ABSTRACT
INTRODUCTION
