The change to less-morbid local therapy for operable breast cancer continues. Systemic induction therapy, whether hormonal therapy or chemotherapy, increases the eligibility for breast-conserving surgery. Sentinel lymph node biopsy (SLNB) has greatly reduced the requirement for axillary dissection, and recent data show that, in addition, whole-breast irradiation can obviate the need for dissection in most patients with clinically node-negative, SLN-positive disease. Although resection margins must be negative for best results, there is no clear evidence that margins exceeding "no ink on tumor" for invasive cancer, or 2 mm for ductal carcinoma in situ, are significantly better. The role of radiation has been clarified, with a clear survival advantage for patients with node-positive disease; however, hypofractionation, which permits a briefer period of treatment, and accelerated partial breast irradiation (APBI) show promise of even further reductions in treatment—although late results for APBI are still needed. Elderly patients (> 70 years) with node-negative disease and estrogen receptor–positive tumors who have been treated with hormonal therapy can avoid primary breast irradiation without significant risk of ultimate breast loss or inferior survival.
Since 1990, death rates from breast cancer have decreased, mainly in women younger than 50 years of age (3.3% per year) vs women aged 50 years or older (2% per year), reflecting the benefit of widespread use of systemic treatment added to early detection.
Improved local control is also causally associated with improved breast cancer survival. An absolute reduction in local recurrence at 5 years is associated in a 4:1 ratio with an absolute survival advantage at 15 years in the overviews of clinical trials. Guidelines for locoregional treatment of breast cancer were first published by the US National Institutes of Health in 1991. Since then, new surgical and radiotherapeutic techniques have been developed, and revised guidelines for locoregional management were suggested in 2008 by the Biedenkopf Expert Panel Members.
Over the past 50 years there have been major changes in the treatment of patients with breast cancer, with "less is more" being the theme. Treatment of breast cancer has evolved dramatically from the Halsted radical mastectomy, and many women now choose breast-conserving surgery and sentinel node biopsy. Breast-conserving surgery (BCS) is defined as the complete removal of the tumor with a concentric margin of surrounding healthy tissue and maintenance of acceptable cosmesis. BCS should be followed by radiation therapy to achieve an acceptably low rate of local recurrence.
In an effort to increase the number of patients eligible for breast conservation, neoadjuvant chemotherapy that shrinks the primary tumor before surgery has become an appealing option. In a large randomized trial, National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-18, investigators randomized 1,523 women with Stage I–IIIa breast cancer to receive doxorubicin (Adriamycin, A) and cyclophosphamide (C) either preoperatively or postoperatively. A reduction in tumor diameter of at least 50% was noted clinically in 80% of the patients, and in 37% no tumor was clinically apparent after chemotherapy. The initial findings of the study were reported at 5 years; in the 9-year follow-up publication, there continued to be no difference in overall survival or disease-free survival in patients receiving chemotherapy preoperatively vs postoperatively. The breast conservation rate was 68% for the neoadjuvant arm and 60% for the adjuvant arm. The reduction in tumor volume allows an improved cosmetic outcome in the majority of patients. Induction chemotherapy followed by BCS and radiation therapy is safe and increases the eligibility for breast preservation in approximately one-fourth of patients with large tumors relative to breast size. From a surgical standpoint, when the neoadjuvant approach is being considered, it is mandatory to insert a radioopaque marker into the tumor in order to localize the surgical site after partial or complete tumor regression.
Another important advantage of neoadjuvant chemotherapy is that it probes the chemosensitivity of the tumor, providing information of great importance in terms of development of systemic treatments for chemoresistant tumors. Tumors exhibiting the characteristics referred to as luminal A (strongly ER-positive, PR-positive, HER2-negative) exhibit less-dramatic reductions in volume with neoadjuvant chemotherapy but will often respond to neoadjuvant therapy with aromatase inhibitors or tamoxifen. Conversely, for HER2-positive tumors, adding trastuzumab (Herceptin) to a standard neoadjuvant regimen achieved a pathologic complete response (pCR) of 65.2%, compared with a 26% pCR in patients who did not receive trastuzumab.
1. Peto R, Boreham J, Clarke M, et al. UK and USA breast cancer deaths down 25% in year 2000 at ages 20-69 years. Lancet. 2000;355:1822.
2. 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. 2005;366:2087-2106.
3. NIH consensus conference. Treatment of early-stage breast cancer. JAMA. 1991;265:391-5.
4. Kaufmann M, Morrow M, von Minckwitz G, et al. Locoregional treatment of primary breast cancer: consensus recommendations from an International Expert Panel. Cancer. 2010;116:1184-91.
5. Bonadonna G, Veronesi U, Brambilla C, et al. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Natl Cancer Inst. 1990;82:1539-45.
6. Wolmark N, Wang J, Mamounas E, et al. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001;96-102.
7. Fisher B, Bryant J, Wolmark N, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672-85.
8. Buzdar AU. Preoperative chemotherapy treatment of breast cancer—a review. Cancer. 2007;110:2394-2407.
9. Taghian A, Mohiuddin M, Jagsi R, et al. Current perceptions regarding surgical margin status after breast-conserving therapy: results of a survey. Ann Surg. 2005;241:629-39.
10. Schnitt SJ, Abner A, Gelman R, et al. The relationship between microscopic margins of resection and the risk of local recurrence in patients with breast cancer treated with breast-conserving surgery and radiation therapy. Cancer. 1994;74:1746-51.
11. Dunne C, Burke JP, Morrow M, Kell MR. Effect of margin status on local recurrence after breast conservation and radiation therapy for ductal carcinoma in situ. J Clin Oncol. 2009;27:1615-20.
12. Singletary SE. Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg. 2002;184:383-93.
13. Smitt MC, Nowels KW, Zdeblick MJ, et al. The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer. 1995;76:259-67.
14. Waljee JF, Hu ES, Newman LA, Alderman AK. Predictors of re-excision among women undergoing breast-conserving surgery for cancer. Ann Surg Oncol. 2008;15:1297-1303.
15. Waljee JF, Hu ES, Newman LA, Alderman AK. Predictors of breast asymmetry after breast-conserving operation for breast cancer. J Am Coll Surg. 2008;
16. Bani MR, Lux MP, Heusinger K, et al. Factors correlating with reexcision after breast-conserving therapy. Eur J Surg Oncol. 2009;35:32-7.
17. Balch GC, Mithani SK, Simpson JF, Kelley MC. Accuracy of intraoperative gross examination of surgical margin status in women undergoing partial mastectomy for breast malignancy. Am Surg. 2005;71:22-7.
18. Olson TP, Harter J, Munoz A, Mahvi DM, et al. Frozen section analysis for intraoperative margin assessment during breast-conserving surgery results in low rates of re-excision and local recurrence. Ann Surg Oncol. 2007;14:2953-60.
19. Saarela AO, Paloneva TK, Rissanen TJ, Kiviniemi HO. Determinants of positive histologic margins and residual tumor after lumpectomy for early breast cancer: a prospective study with special reference to touch preparation cytology. J Surg Oncol. 1997; 66:248-53.
20. Rizzo M, Iyengar R, Gabram SG, et al. The effects of additional tumor cavity sampling at the time of breast-conserving surgery on final margin status, volume of resection, and pathologist workload. Ann Surg Oncol. 2010;17:228-34.
21. Lotze MT, Duncan MA, Gerber LH, et al. Early versus delayed shoulder motion following axillary dissection: a randomized prospective study. Ann Surg. 1981;193:288-95.
22. Ivens D, Hoe AL, Podd TJ, et al. Assessment of morbidity from complete axillary dissection. Br J Cancer. 1992;66:136-8.
23. Port ER, Patil S, Stempel M, et al. Number of lymph nodes removed in sentinel lymph node-negative breast cancer patients is significantly related to patient age and tumor size: a new source of bias in morbidity assessment? Cancer. 2010;116:1987-91.
24. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569-75.
25. 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. 2002;347:1227-32.
26. 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. 2002;347:1233-41.
27. Polgar C, Major T. Current status and perspectives of brachytherapy for breast cancer. Int J Clin Oncol. 2009;14:7-24.
28. Shaitelman SF, Vicini FA, Beitsch P, et al. Five-year outcome of patients classified using the American Society for Radiation Oncology consensus statement guidelines for the application of accelerated partial breast irradiation: an analysis of patients treated on the American Society of Breast Surgeons MammoSite Registry Trial. Cancer. 2010;116:4677-85.
29. Vicini F, Arthur D, Wazer D, et al. Limitations of the American Society of Therapeutic Radiology and Oncology Consensus Panel guidelines on the use of accelerated partial breast irradiation. Int J Radiat Oncol Biol Phys. 2011;79:977-84.
30. Albuquerque K, Janusek L, Mathews H, et al. Short-term quality of life following partial breast irradiation with balloon brachytherapy—comparison with whole breast irradiation. Breast J. 2010;16:325-6.
31. Wadasadawala T, Budrukkar A, Chopra S, et al. Quality of life after accelerated partial breast irradiation in early breast cancer: matched pair analysis with protracted whole breast radiotherapy. Clin Oncol (R Coll Radiol). 2009;21:668-75.
32. 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. 2004;351:971-7.
33. Hughes KS, Schnaper LA, Cirrincione C, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 or older with early breast cancer (abstract). J Clin Oncol. 2010;28(suppl 15S):507.
34. Whelan TJ, Pignol JP, Julian J, et al. Long-term results of a randomized trial of accelerated hypofractionated whole breast irradiation following breast conserving surgery in women with node-negative breast cancer (abstract).Int J Radiat Oncol Biol Phys.2008;72(suppl 28):A60.