Prior to the 1970s, the treatment of breast cancer was dominated by radical mastectomy or modified radical mastectomy of the affected breast . This consists of an en bloc removal of the breast, muscles of the chest wall, and contents of the axilla and was advocated as the most appropriate local therapy for women with early-stage breast cancers. However, the results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 trial and other studies, found equivalent survival and local control rates among women treated with breast-conservation therapy (BCT)—either mastectomy or lumpectomy followed by whole-breast irradiation (WBI).[3,4] The NSABP B-06 trial, which compared mastectomy to lumpectomy with and without radiotherapy in women with invasive carcinoma, found a 39% local recurrence rate at 20 years with lumpectomy alone, which was decreased to 14% with the addition of radiotherapy. Several other randomized studies demonstrated equivalent long-term survival and disease-free survival rates in patients treated by BCT compared to mastectomy.[2-5]
Additional randomized studies comparing lumpectomy alone to lumpectomy and radiation clearly demonstrate a threefold reduction in local relapse with the use of radiation following breast-conserving surgery.[6-10] More recent meta-analysis of trials comparing lumpectomy alone to lumpectomy and radiation demonstrated not only a threefold higher local relapse rate with the omission of radiation following lumpectomy, but also a small yet statistically significant compromise in overall survival.[11,12] For patients with ductal carcinoma in situ (DCIS), randomized studies comparing lumpectomy alone to lumpectomy plus radiation, conducted by the NSABP and European Organisation for Research and Treatment of Cancer (EORTC), found a 55% and 43% reduction in ipsilateral breast cancer events, respectively, with the addition of radiotherapy.[13,14]
As a result of these data, breast-conservation surgery followed by whole-breast irradiation (BCS+RT) became the standard of care for women with stage 0, I, and II breast cancer. BCS+RT involves the surgical removal of the primary tumor, evaluation of the axillary nodes, followed by whole-breast irradiation. This treatment is extremely well tolerated with minimal long-term complications and favorable cosmetic outcomes.[15,16] Despite the obvious cosmetic and potential psychosocial advantages of BCS+RT, 15% to 30% of patients who undergo lumpectomy do not receive postoperative radiotherapy.[17-20] Many patients may choose mastectomy or lumpectomy alone over BCS+RT due to the protracted course of daily treatment involved with WBI, which consists of daily radiotherapy to the whole breast for 25 treatments usually followed by a boost to the tumor bed, delivered over the course of 6 to 6.5 weeks.[21,22] Other reasons that may steer women away from BCS+RT have been identified as physician bias, patient age, fear of radiation treatments, distance from a radiation treatment facility, and socioeconomic factors.[20,23,24]
Search for an Alternative to WBI
Based on the numerous randomized studies noted above, it is standard of care for all women, regardless of age or tumor size, to receive radiotherapy in the setting of BCT to reduce local recurrence. However, in recent years, investigators have tried to identify subsets of women who may not benefit from the addition of radiotherapy to lumpectomy for early-stage breast cancer.
A prospective study from the Cancer and Leukemia Group B (CALGB) randomized women 70 years of age or older with tumors that were estrogen-receptor-positive and less than 2 cm in diameter to tamoxifen with or without radiotherapy. In this randomized trial, even though radiotherapy significantly reduced the rate of local recurrence (from 4% to 1%), there was no difference in overall survival, and the investigators concluded that "tamoxifen alone is a reasonable choice for adjuvant treatment in such women." Published simultaneously, a Canadian trial in women over age 50 with early-stage breast cancer demonstrated a local relapse rate of 7.7% with lumpectomy and tamoxifen compared to 0.6% with lumpectomy, tamoxifen, and radiation. Although there was no compromise in survival with the omission of radiation in either trial, these studies were not powered sufficiently to detect small benefits in survival.
Smith et al, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, identified 8,724 women over age 70 years who met the eligibility criteria for CALGB 9343. They compared those women over age 70 treated with radiotherapy following lumpectomy to those treated by lumpectomy alone. In this nonrandomized study, they found that radiotherapy not only reduced local recurrence but also reduced the rate of any second breast cancer event and subsequent mastectomy. They further identified subgroups, such as women between 70 and 79 years with low comorbidities and those with lobular histology, who derived the greatest benefit from radiotherapy. Of note, in the SEER-Medicare database of women age 70 or greater, only 59% of patients treated with breast-conserving surgery received radiation.
Collectively, these data suggest that for older women, although radiation may be safely avoided, it is rational for elderly women with long life expectancies and low comorbidities to receive radiotherapy after lumpectomy, given its benefit. However, many fail to do so in light of the prolonged course of therapy, resources involved in travel, and distance to a radiotherapy center.
Introduction of APBI
In response, accelerated partial-breast irradiation (APBI) has been studied increasingly over the past 15 years as a viable alternative to WBI. In general, APBI involves treating the surgical cavity with a 1- to 2-cm margin, thus reducing the volume of irradiated breast tissue by up to 50% using various radiotherapeutic methods. Technical approaches of partial-breast irradiation include multicatheter interstitial brachytherapy, balloon catheter brachytherapy, three-dimensional conformal external-beam radiotherapy (3D-CRT) and intraoperative radiotherapy (IORT). Treatment is typically delivered postoperatively, over a short period of time, using large fraction sizes.
Advocates of APBI state that it is a safe, well tolerated therapy that allows for equivalent cosmetic outcomes while significantly increasing quality of life and allowing for an effective treatment of the patient's breast cancer. To date, pilot studies of various APBI techniques have been studied, and large, multicenter, randomized controlled studies are underway comparing APBI to WBI.
In standard BCS+RT, radiotherapy is delivered to the whole breast to eliminate areas of occult multicentric in situ or invasive carcinoma. Additional radiotherapy may be delivered to the tumor bed using a boost to eliminate the higher burden of microscopic disease that may have been left in close proximity to the tumor bed after lumpectomy.
Following BCS and whole-breast irradiation, the majority of local relapses occur in close proximity to the tumor bed. When discussing a tumor recurrence in the ipsilateral breast, it is important to note the difference between a true recurrence and the development of a second primary in the irradiated breast. A study from Yale described the development of a new primary when the recurrence was distinctly different from the primary tumor with respect to the histologic subtype, location, or ploidy. In their studies of patients treated with BCT with 15 year data,[27,28] patients developed both true recurrences and new primaries at similar rates until approximately 8 years, when true recurrence rates stabilized but new primary rates continued to rise.
Recht et al also found that the majority of true recurrences occurred in the first 5 to 10 years, but with increasing follow-up, they saw a higher incidence of second primary tumors that developed in other quadrants of the breast. The 20-year update from Veronesi et al comparing mastectomy to BCT showed a nonsignificant difference between the development of new primaries in the ipsilateral breast (0.42 per 100 woman-years of observation) treated with BCT compared with the contralateral breast (0.63 per 100 woman-years of observation).
Several retrospective as well as prospective studies evaluating patterns of local relapse following BCS with or without radiation have shown that the majority of tumor recurrences occurred at or near the original tumor bed.[30,31] Veronesi et al found that failures beyond the lumpectomy cavity occurred in 2.9% of patients, consistent with previously published data of 1.5% and 3.5%,[11,32,33] These data suggest that the true benefit to radiotherapy may be to decrease the recurrence of tumor at or near the tumor bed, but may not prevent the development of new, second primary breast cancers that may occur elsewhere in the irradiated breast.
Anatomic data on the distribution of tumor cells in relation to the primary lesion have been published in surgical series. Holland et al reviewed 217 mastectomy specimens from patients in the Netherlands with tumors less than 4 cm. They reported that the presence of an extensive intraductal component (EIC) was associated with a substantial likelihood of having residual disease located beyond a 2-cm margin from the primary tumor, whereas in patients without an EIC, it was rare for cancer foci to be found more than 2 cm from the primary tumor.
In a recent abstract presented at the European Society for Therapeutic Radiation Oncology (ESTRO) meeting in 2006, Holland studied pathologic and mammographic criteria to identify breast carcinomas of limited extent, defined as an absence of microcalcifications or tumor density beyond the edge of the primary lesion based on mammography and a 1-cm tumor-free margin out of a 2-cm gross surgical margin based on pathology. The group found that 89% of patients who met these criteria were correctly identified as having a true breast carcinoma of limited extent. The authors concluded that by carefully examining radiographic and pathologic data, one may be able to correctly identify patients who may be candidates for "surgical excision of the tumor followed by partial-breast irradiation."
The fact that a majority of true local relapses occur in close proximity to the tumor bed, along with available pathologic data demonstrating minimal microscopic tumor burden more than 1 to 2 cm beyond the primary tumor, provides a rationale for more localized treatment in selected patients. With APBI, a conformal dose of radiation is delivered to a limited volume of breast in a short period of time. Unfortunately, the majority of data regarding APBI involves single-institution, nonrandomized studies with small patient populations. While these data are promising, it is clear that to firmly establish APBI as an acceptable alternative to WBI, prospective randomized studies are necessary. Recently, an intergroup trial (NSABP/Radiation Therapy Oncology Group [RTOG]) launched a large randomized study comparing WBI to APBI for women with early-stage invasive and noninvasive breast cancer. Accrual has been brisk and is expected to close earlier than expected.
The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
1. Fisher B, Anderson S, Bryant J, et al: Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233-1241, 2002.
2. Veronesi U, Cascinelli N, Mariani L, et al: Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227-1232, 2002.
3. Blichert-Toft M, Rose C, Andersen JA, et al: Danish randomized trial comparing breast conservation therapy with mastectomy: Six years of life-table analysis. Danish Breast Cancer Cooperative Group. J Natl Cancer Inst Monogr 19-25, 1992.
4. Poggi MM, Danforth DN, Sciuto LC, et al: Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy: The National Cancer Institute randomized trial. Cancer 98:697-702, 2003.
5. van Dongen JA, Voogd AC, Fentiman IS, et al: Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 92:1143-1150, 2000.
6. Clark RM, Whelan T, Levine M, et al: Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: An update. Ontario Clinical Oncology Group. J Natl Cancer Inst 88:1659-1664, 1996.
7. Fisher B, Bryant J, Dignam JJ, et al: Tamoxifen, radiation therapy, or both for prevention of ipsilateral breast tumor recurrence after lumpectomy in women with invasive breast cancers of one centimeter or less. J Clin Oncol 20:4141-4149, 2002.
8. Liljegren G, Holmberg L, Bergh J, et al: 10-year results after sector resection with or without postoperative radiotherapy for stage I breast cancer: A randomized trial. J Clin Oncol 17:2326-2333, 1999.
9. Veronesi U, Marubini E, Mariani L, et al: Radiotherapy after breast-conserving surgery in small breast carcinoma: Long-term results of a randomized trial. Ann Oncol 12:997-1003, 2001.
10. Winzer KJ, Sauer R, Sauerbrei W, et al: Radiation therapy after breast-conserving surgery; first results of a randomised clinical trial in patients with low risk of recurrence. Eur J Cancer 40:998-1005, 2004.
11. Clarke M, Collins R, Darby S, et al: 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.
12. Vinh-Hung V, Verschraegen C: Breast-conserving surgery with or without radiotherapy: Pooled-analysis for risks of ipsilateral breast tumor recurrence and mortality. J Natl Cancer Inst 96:115-121, 2004.
13. Fisher B, Dignam J, Wolmark N, et al: Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 16:441-452, 1998.
14. Julien JP, Bijker N, Fentiman IS, et al: Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: First results of the EORTC randomised phase III trial 10853. EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. Lancet 355:528-533, 2000.
15. Vrieling C, Collette L, Fourquet A, et al: The influence of the boost in breast-conserving therapy on cosmetic outcome in the EORTC "Boost Versus No Boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer. Int J Radiat Oncol Biol Phys 45:677-685, 1999.
16. Vrieling C, Collette L, Fourquet A, et al: The influence of patient, tumor and treatment factors on the cosmetic results after breast-conserving therapy in the EORTC 'Boost vs No Boost' trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. Radiother Oncol 55:219-232, 2000.
17. Farrow DC, Hunt WC, Samet JM: Geographic variation in the treatment of localized breast cancer. N Engl J Med 326:1097-1101, 1992.
18. Lazovich DA, White E, Thomas DB, et al: Underutilization of breast-conserving surgery and radiation therapy among women with stage I or II breast cancer. JAMA 266:3433-3438, 1991.
19. Mann BA, Samet JM, Hunt WC, et al: Changing treatment of breast cancer in New Mexico from 1969 through 1985. JAMA 259:3413-3417, 1988.
20. Ballard-Barbash R, Potosky AL, Harlan LC, et al: Factors associated with surgical and radiation therapy for early stage breast cancer in older women. J Natl Cancer Inst 88:716-726, 1996.
21. Kelemen JJ 3rd, Poulton T, Swartz MT, et al: Surgical treatment of early-stage breast cancer in the Department of Defense healthcare system. J Am Coll Surg 192:293-297, 2001.
22. Whelan T, Levine M, Gafni A, et al: Mastectomy or lumpectomy? Helping women make informed choices. J Clin Oncol 17:1727-1735, 1999.
23. Athas WF, Adams-Cameron M, Hunt WC, et al: Travel distance to radiation therapy and receipt of radiotherapy following breast-conserving surgery. J Natl Cancer Inst 92:269-271, 2000.
24. Schroen AT, Brenin DR, Kelly MD, et al: Impact of patient distance to radiation therapy on mastectomy use in early-stage breast cancer patients. J Clin Oncol 23:7074-7080, 2005.
25. Hughes KS, Schnaper LA, Berry D, et al: Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351:971-977, 2004.
26. Smith BD, Gross CP, Smith GL, et al: Effectiveness of radiation therapy for older women with early breast cancer. J Natl Cancer Inst 98:681-690, 2006.
27. Obedian E, Fischer DB, Haffty BG: Second malignancies after treatment of early-stage breast cancer: Lumpectomy and radiation therapy versus mastectomy. J Clin Oncol 18:2406-2412, 2000.
28. Smith TE, Lee D, Turner BC, et al: True recurrence vs. New primary ipsilateral breast tumor relapse: An analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management. Int J Radiat Oncol Biol Phys 48:1281-1289, 2000.
29. Recht A, Come, SE, Troyan, S, et al: Local-regional recurrence after mastectomy or breast-conserving therapy, in Harris JR, Lippman ME, Morrow M, et al (eds): Diseases of the Breast, 2nd ed, pp 731-748. Philadelphia, Lippincott Williams & Wilkins, 2000.
30. Fisher B, Anderson S: Conservative surgery for the management of invasive and noninvasive carcinoma of the breast: NSABP trials. National Surgical Adjuvant Breast and Bowel Project. World J Surg 18:63-69, 1994.
31. Holli K, Saaristo R, Isola J, et al: Lumpectomy with or without postoperative radiotherapy for breast cancer with favourable prognostic features: Results of a randomized study. Br J Cancer 84:164-169, 2001.
32. Sector resection with or without postoperative radiotherapy for stage I breast cancer: A randomized trial. The Uppsala-Orebro Breast Cancer Study Group. J Natl Cancer Inst 82:1851, 1990.
33. Clark RM, McCulloch PB, Levine MN, et al: Randomized clinical trial to assess the effectiveness of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer. J Natl Cancer Inst 84:683-689, 1992.
34. Holland R, Connolly JL, Gelman R, et al: The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast. J Clin Oncol 8:113-118, 1990.
35. Holland R: Pathological target definition in patients selected for APBI (abstract 170). Radiother Oncol 81(suppl 1):S65-S66, 2006.
36. Arthur DW, Vicini FA, Kuske RR, et al: Accelerated partial breast irradiation: An updated report from the American Brachytherapy Society. Brachytherapy 2:124-130, 2003.
37. 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.
38. 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.
39. Zwicker RD, Arthur DW, Kavanagh BD, et al: Optimization of planar high-dose-rate implants. Int J Radiat Oncol Biol Phys 44:1171-1177, 1999.
40. Kuske RR, Bolton J, Wilenzick RM, et al: Brachytherapy as the sole method of breast irradiation in Tis, T1, T2, N0-1 breast cancer (abstract). Int J Radiat Oncol Biol Phys 30:245, 1994.
41. King TA, Bolton JS, Kuske RR, et al: Long-term results of wide-field brachytherapy as the sole method of radiation therapy after segmental mastectomy for T(is,1,2) breast cancer. Am J Surg 180:299-304, 2000.
42. Vicini FA, Kestin L, Chen P, et al: Limited-field radiation therapy in the management of early-stage breast cancer. J Natl Cancer Inst 95:1205-1210, 2003.
43. Kuske RR, Winter K, Arthur DW, et al: A phase I/II trial of brachytherapy alone following lumpectomy for select breast cancer: Toxicity analysis of Radiation Therapy Oncology Group 95-17 (abstract). Int J Radiat Oncol Biol Phys 54:87, 2002.
44. Arthur DW, Winter K, Kuske RR, et al: A phase II trial of brachytherapy alone following lumpectomy for select breast cancer: Tumor control and survival outcomes of RTOG 95-17 (abstract). Int J Radiat Oncol Biol Phys 66:S29-S30, 2006.
45. Fentiman IS, Deshmane V, Tong D, et al: Caesium(137) implant as sole radiation therapy for operable breast cancer: A phase II trial. Radiother Oncol 71:281-285, 2004.
46. Fentiman IS, Poole C, Tong D, et al: Iridium implant treatment without external radiotherapy for operable breast cancer: A pilot study. Eur J Cancer 27:447-450, 1991.
47. Poti Z, Nemeskeri C, Fekeshazy A, et al: Partial breast irradiation with interstitial 60co brachytherapy results in frequent grade 3 or 4 toxicity. Evidence based on a 12-year follow-up of 70 patients. Int J Radiat Oncol Biol Phys 58:1022-1033, 2004.
48. Polgar C, Fodor J, Major T, et al: Radiotherapy confined to the tumor bed following breast conserving surgery current status, controversies, and future projects. Strahlenther Onkol 178:597-606, 2002.
49. Polgar C, Major T, Somogyi A, et al: Sole brachytherapy of the tumor bed after breast conserving surgery: A new radiotherapeutic strategy for patients at low risk of local relapse. Neoplasma 46:182-189, 1999.
50. Polgar C, Major T, Fodor J, et al: High-dose-rate brachytherapy alone versus whole breast radiotherapy with or without tumor bed boost after breast-conserving surgery: Seven-year results of a comparative study. Int J Radiat Oncol Biol Phys 60:1173-1181, 2004.
51. Zannis V, Beitsch P, Vicini F, et al: Descriptions and outcomes of insertion techniques of a breast brachytherapy balloon catheter in 1403 patients enrolled in the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry trial. Am J Surg 190:530-538, 2005.
52. Keisch ME, Vicini FA, Beitsch P, et al: Two year actuarial analysis of 198 patients with dcis treated with accelerated partial breast irradiation (APBI): Efficacy, cosmesis and toxicity in patients on the American Society of Breast Surgeons (ASBS) MammoSite Breast Brachytherapy Registry trial. Int J Radiat Oncol Biol Phys 66:S213, 2006.
53. Cuttino LW, Arthur DW, Keisch M, et al: Multi-institutional experience using the MammoSite Radiation Therapy System (RTS) in the treatment of early-stage breast cancer: 2 year results. Int J Radiat Oncol Biol Phys 66:S30-S31, 2006.
54. Benitez PR, Streeter O, Vicini F, et al: Preliminary results and evaluation of MammoSite balloon brachytherapy for partial breast irradiation for pure ductal carcinoma in situ: A phase II clinical study. Am J Surg 192:427-433, 2006.
55. Ellerin BE, Seidenfeld J, Formenti SC: A systematic review of post-lumpectomy radiation therapy regimens (abstract 683). Proc Am Soc Clin Oncol 23:47, 2004
56. Suh WW, Pierce LJ, Vicini FA, et al: A cost comparison analysis of partial versus whole-breast irradiation after breast-conserving surgery for early-stage breast cancer. Int J Radiat Oncol Biol Phys 62:790-796, 2005.
57. Baglan KL, Sharpe MB, Jaffray D, et al: Accelerated partial breast irradiation using 3D conformal radiation therapy (3D-CRT). Int J Radiat Oncol Biol Phys 55:302-311, 2003.
58. Vicini FA, Remouchamps V, Wallace M, et al: Ongoing clinical experience utilizing 3d conformal external beam radiotherapy to deliver partial-breast irradiation in patients with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys 57:1247-1253, 2003.
59. Vicini F, Winter K, Straube W, et al: A phase I/II trial to evaluate three-dimensional conformal radiation therapy confined to the region of the lumpectomy cavity for stage i/ii breast carcinoma: Initial report of feasibility and reproducibility of Radiation Therapy Oncology Group (RTOG) study 0319. Int J Radiat Oncol Biol Phys 63:1531-1537, 2005.
60. Wernicke AG, Gidea-Addeo D, Magnolfi C, et al: External beam partial breast irradiation following breast-conserving surgery: Preliminary results of cosmetic outcome of NYU 00-23 (abstract 54). Int J Radiat Oncol Biol Phys 66(suppl S):S32, 2006.
61. Hall E: Radiobiology for the Radiologist, 5th ed. Philadelphia, Lippincott Williams & Wilkins, 2000.
62. Vaidya JS, Tobias JS, Baum M, et al: Intraoperative radiotherapy for breast cancer. Lancet Oncol 5:165-173, 2004.
63. Veronesi U, Gatti G, Luini A, et al: Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery. Arch Surg 138:1253-1256, 2003.
64. Tobias JS, Vaidya JS, Keshtgar M, et al: Reducing radiotherapy dose in early breast cancer: The concept of conformal intraoperative brachytherapy. Br J Radiol 77:279-284, 2004.
65. Huang J, Barbera L, Brouwers M, et al: Does delay in starting treatment affect the outcomes of radiotherapy? A systematic review. J Clin Oncol 21:555-563, 2003.
66. Bellon JR, Come SE, Gelman RS, et al: Sequencing of chemotherapy and radiation therapy in early-stage breast cancer: Updated results of a prospective randomized trial. J Clin Oncol 23:1934-1940, 2005.
67. Obedian E, Haffty BG: Negative margin status improves local control in conservatively managed breast cancer patients. Cancer J Sci Am 6:28-33, 2000.
68. 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.
69. Berle L, Wazer DE, Graham R, et al: Toxicity, local control and cosmesis after interstitial partial breast HDR brachytherapy alone for T1/T2 breast cancer (abstract 74). Radiother Oncol 71(suppl):S37, 2004.
70. Arthur DW, Koo D, Zwicker RD, et al: Partial breast brachytherapy after lumpectomy: Low-dose-rate and high-dose-rate experience. Int J Radiat Oncol Biol Phys 56:681-689, 2003.
71. Zellars R, Frassica D, Stearns V, et al: Partial breast irradiation (PBI) concurrent with adjuvant dose-dense doxorubicin and cyclophosphamide (ddac) chemotherapy in early-stage breast cancer: Preliminary safety results from a feasibility trial (abstract 10675). J Clin Oncol 24(18S):582s, 2006.
72. Haffty BG, Vicini FA, Beitsch P, et al: Timing of chemotherapy following accelerated partial breast irradiation: Analysis of the American Society of Breast Surgeons MammoSite registry trial (abstract 4081). Breast Cancer Res Treat 100(suppl 1), 2006.