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Journal of Clinical Oncology, Vol 23, No 8 (March 10), 2005: pp. 1685-1697 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.09.046
Advances in Breast Conservation Therapy
From the Department of Surgery, University of Michigan, Ann Arbor, MI; and Department of Surgical Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX Address reprint requests to Lisa A. Newman, MD, MPH, FACS, Breast Care Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109; e-mail: lanewman{at}umich.edu.
Breast conservation therapy (BCT) is now well established as oncologically safe treatment for primary breast cancer, and in fact has been deemed the preferable surgical option in a 1991 National Cancer Institute (NCI) position statement1 on management of early-stage disease. This consensus was reached after the completion of several prospective, randomized clinical trials confirming survival equivalence in breast cancer patients randomly assigned to receive BCT versus mastectomy. Follow-up as long as 20 years has been reported (Table 1) as well as a meta-analysis of all trials,10 with stability of the outcome results.
Reports from the National Cancer Database and comparisons to practice patterns in England demonstrate that BCT tends to be underutilized in the United States,11,12 with rates ranging from less than 10% to 45%. Factors associated with increased likelihood of breast preservation include young age13-16; treatment in the northeast compared to southern regions14,16,17; affluent socioeconomic status14; and treatment in metropolitan areas associated with a cancer center14 or teaching hospital.15,17 Recently, Lucci et al18 presented provocative data suggesting that the excessive mastectomy rates in the United States might also be related to the third party payors' lower reimbursement scale for lumpectomy codes.
Eligibility and Exclusion Criteria for BCT Radiation therapy is a necessary adjunct to lumpectomy as a means of treating microscopic foci of multifocal and multicentric cancer, thereby minimizing risk of local recurrence. As demonstrated by the 20-year follow-up results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-06 study,2 local recurrence is decreased from 39% to 14% by the delivery of radiation after lumpectomy. The B-06 trial and other studies of lumpectomy with versus without radiation therapy2,19-23 have revealed comparable survival rates for these arms, leading to the widespread belief that adjuvant XRT does not contribute to survival. This concept has recently been challenged, however, on the basis of established outcome benefits associated with postmastectomy XRT in high-risk patients24; by extrapolation it can be argued that optimization of local control in the breast after lumpectomy by the addition of XRT will also improve survival. Support for this hypothesis is generated by findings from a meta-analysis conducted by Vinh-Hung and Verschraegen,25 where results were pooled from all prospective, randomized clinical trials of lumpectomy alone versus lumpectomy and breast XRT. This study revealed a statistically significant 8.6% survival benefit associated with postlumpectomy XRT. Guidelines from the American College of Radiology and the American College of Surgeons26 provide a general framework for identifying and managing BCT candidates: (1) unifocal disease is preferred; (2) diffuse, malignant-appearing microcalcifications on the preoperative mammogram contraindicate BCT. This frequently correlates with diffuse ductal carcinoma-in-situ, precluding the ability to achieve negative margins. If the volume of calcifications in comparison to the breast size is thought to be amenable to a successful lumpectomy, then mammographic guidance for the insertion of two or more localization bracketing wires may facilitate the effort. Postlumpectomy mammography must document absence of residual calcifications prior to delivery of XRT, even if the lumpectomy margins are negative. BCT in cases of indeterminate calcifications should be considered with caution; whenever possible the calcifications should be resected en bloc with the tumor. If the calcifications are remote from the primary tumor site, then breast preservation should only be undertaken if the radiologist is confident of benignity based on diagnostic views, and if mammographic follow-up appears safe; (3) prior therapeutic chest irradiation is a contraindication to BCT if the breast is within the prior treatment field. This is relevant for Hodgkin's disease patients treated with chest-wall XRT during adolescence/early adulthood because of the increased risk of radiation-induced breast cancers that appear two to three decades after treatment; (4) radiation therapy is contraindicated during pregnancy because of scatter exposure to the fetus; (5) positive lumpectomy margins. There is no predefined limit on the number of resections that should be attempted in seeking margin control, but multiple unsuccessful re-excisions may indicate an excessive breast tumor burden, delay administration of postoperative adjuvant therapy, and compromise cosmesis; (6) history of particular collagen vascular disease such as scleroderma (but not rheumatoid arthritis) is a relative contraindication to BCT because of radiation toxicity risks; (7) primary tumor size should be less than 5 cm, as the phase III BCT clinical trials were limited to T1 and T2 lesions. Larger tumors by definition require larger volume lumpectomies; this can make XRT planning more challenging and threatens the aesthetic result. The ratio of tumor-to-breast size should also be taken into account.
Family History Family history has been investigated as a possible risk factor for BCT failure because of initial concerns that a genetic predisposition to breast cancer might increase the likelihood of subsequent neoplastic events in the treated breast. Several studies27-29 have investigated this question, and in each case, family history did not increase the risk of local recurrence following BCT for breast cancer. Patients with a strong family history, however, are often found to have a higher risk for developing new primary breast tumors.27,28
Primary Lobular Histology and/or Coexisting LCIS Retrospective, prospective, and case-control studies have now shown that invasive lobular cancers30-35 and cases of LCIS coexisting with an invasive cancer36-38 can be safely managed with breast preservation. The presence of LCIS at the lumpectomy margin is irrelevant. Some investigators have noted that invasive lobular lesions39 and infiltrating tumors coexisting with LCIS40 have an increased risk of in-breast events, but in both scenarios the excess breast events tend to occur over a protracted follow-up. This suggests an increased long-term risk of developing new primary breast lesion.
Margin Status Although margin status has been repeatedly (but not invariably) associated with local control in conservatively treated breast cancer, there is no universally accepted definition for the optimal tumor-free margin. A common approach in clinical practice is to resect the breast tumor with an approximately 1-cm-thick rim of surrounding tissue with the expectation that this will yield a microscopic margin of at least 1 to 5 mm on pathologic analysis. The oncologic priority of maximizing local control must be weighed against the desire to optimize the cosmetic result, which will depend on volume of resected breast tissue. As shown in Table 1, even the phase III BCT trials have varied substantially in defining a negative margin. The NSABP requires absence of tumor cells at the inked specimen edge; the NCI trial of BCT did not mandate microscopic margin negativity at all. The concept that wider margins reduce LR risk was shown by the Milan Cancer Institute54-56 where quadrantectomy (involving removal of 2- to 3-cm tissue surrounding the breast tumor en bloc with overlying skin and underlying fascia) was compared to tumorectomy (lumpectomy aimed at removal of gross tumor mass only, with no effort made to clear surrounding microscopic disease) for 705 patients with cancers up to 2.5 cm in size. Both arms received 45-Gy breast XRT and a 15-Gy boost dose. Although actuarial survival curves were identical for the two arms of the study at 7 years, there were fewer local recurrences in the quadrantectomy arm (5.3%) compared with the tumorectomy arm (13.3%). Pathologic margin assessment revealed positivity in eight of 178 assessable quadrantectomy cases (4.5%), and in 46 (16%) of 289 assessable tumorectomy cases. The LR rates were similarly elevated in these two groups of margin-positive patients (12.5% v 17.4%). It is clear that tumors should not be transected, leaving gross residual disease. However a single microscopically close or involved margin focus may not necessarily increase the local recurrence risk substantially, especially if followed by a radiation boost dose.43,48,57 In general, a microscopic margin of at least 2 mm seems to insure reasonable likelihood that that local failure rates will be less than 5% at 5 years.58-60 To some extent, the margin issue is a sampling one, since technical limitations preclude the feasibility of complete microscopic analysis of the entire lumpectomy specimen surface area. If the margin sampling catches a single focus where a tumor abuts the edge of an otherwise widely negative lumpectomy specimen, this probably identifies a breast with a lower microscopic tumor burden compared to a lumpectomy specimen where multiple foci of cancer cells approach several aspects of the lumpectomy surface. As summarized by Gould and Robinson,61 variation between pathologists in the processing, interpretation, and reporting of margins may also influence results.
Extensive Intraductal Component The extensive intraductal component (EIC) has since come to be accepted as a significant risk factor for local recurrence and is commonly defined as tumors having at least 25% DCIS within the primary lesion, as well as DCIS present in adjacent breast tissue. As demonstrated by Holland et al,63 EIC is a marker for patients with a diffuse microscopic cancer burden within the breast, a feature that hinders efforts to obtain margin control, and limits the likelihood of successful breast XRT. Several investigators have confirmed the increased local failure rates (averaging 25% at 5 years) in BCT cases characterized by the presence of EIC.36,42,43,47,58,64-66 Aggressive attempts to optimize margin control may compensate for the elevated risk expressed by an EIC-positive tumor. Schnitt et al67 reported outcome for 181 BCT cases from the JCRT where rigorous margin re-evaluation was possible; median follow-up was 86 months. The 5-year LR was 20% for EIC-positive tumors compared to 7% for EIC-negative lesions. However, subset analysis of the EIC-positive cases revealed that when the final microscopic margins were clear there were no recurrences, compared to 50% of the EIC-positive cases experiencing LR if the margins were more than focally positive. Similarly, Anscher et al68 and Smitt et al69 both found that EIC failed to be a significant predictor of local failure after controlling for margin status in multivariate analysis. The prevailing opinion, therefore, is that EIC-positive disease can be managed safely with breast preservation as long as margin control is achieved.
Young Age
Advanced Breast Imaging and BCT Breast magnetic resonance imaging (MRI) is increasingly being used, and has been reported to have sensitivity approaching 100% in detecting breast cancer.74 It is therefore potentially valuable in ruling out multicentric lesions, defining the extent of a primary breast tumor, and it is now standard-of-care management in screening patients with axillary metastases from an occult primary for breast preservation.75-79 Tan et al,80 Fischer et al,81 and Lee et al82 reported that breast MRI findings altered breast cancer management in 18%, 14%, and 30% of cases, respectively. MRI has also been reported to be particularly useful in defining extent of invasive lobular cancers, and determining eligibility of these cases for breast-conserving surgery. Rodenko et al83 found that MRI-assessment of invasive lobular tumor size correlated with pathology findings in 85% of 20 cases, compared to mammography correlation in only 32%; Schelfout et al84 reported similar success with MRI guidance in cases of invasive lobular carcinoma. Specialized forms of computed tomography (CT) scanning have been developed for breast imaging and are being used for distinguishing patients with unicentric disease from those with multicentric lesions in hopes of optimizing the selection of BCT candidates. Uematsu et al85 reported that use of three-dimensional helical CT images to plan lumpectomy volumes resulted in an approximate halving of the positive margin rate. This technique has also been reported to improve success with lumpectomies performed for invasive lobular cancer. Breast ultrasonography has become a routine adjunct in preoperative breast cancer imaging, and its applications have been expanded to the intraoperative setting. Henry-Tillman et al86 reported that of 25 breast cancers excised with intraoperative ultrasound guidance, negative margins were obtained in 92%. Rahusen et al87 reported similar success with intraoperative ultrasound facilitating lumpectomy performance, and demonstrated its superiority over standard wire localization for achieving margin control in a prospective, randomized study of 49 breast cancer patients requiring image-guidance for lumpectomy. A major disadvantage of intraoperative ultrasound is the requirement for either specialized surgical training or the availability and flexibility of a committed radiologist. Sonographic imaging of the breast has typically been implemented as a targeted study of a breast segment, directed by some clinical or mammographic finding. Whole-breast ultrasound, however, is now being utilized for breast cancer screening in high-risk women because of its advantages in imaging dense tissue. A natural progression was therefore to evaluate the known cancer-containing breast for multicentric disease. Similar to studies of MRI to detect multicentric disease, whole-breast ultrasound has been used to evaluate breast cancer patients prior to definitive surgery, and reported findings have influenced therapy in approximately 15% of cases.88,89 Choosing between these imaging modalities can be a dilemma, but this will largely be resolved by availability of institutional resources. Comparative analyses of these various tests in newly diagnosed breast cancer patients suggest that ultrasound and breast MRI contribute similar added-value to a high-quality mammographic evaluation.88,90 Hata et al91 found that in a series of 183 breast cancers, MRI and breast ultrasound were equivalent diagnostic modalities for detecting breast tumors, but MRI was superior to ultrasound in detecting microscopic extent of disease and intraductal spread. Integrating any of these specialized imaging modalities into the work-up of lumpectomy candidates can increase treatment costs, and expertise with the various technologies is not widely available. Furthermore, we are obligated to define the implications associated with whatever findings are generated. The latter issue, in particular, has not been completely addressed.92 As noted previously, postlumpectomy adjuvant radiation therapy is quite effective in controlling microscopic foci of multifocal/multicentric disease. Some of the tumor foci that are being identified through sophisticated breast imaging may represent sites of disease that would have been effectively treated with radiation. A clinical trial of BCT patients, designed to study this question prospectively with blinding from imaging results, would be a valuable but challenging contribution.
Genetic Testing for Hereditary Breast Cancer Susceptibility In one of the earliest studies, Robson et al93 evaluated 305 Ashkenazi breast cancer patients treated with BCT and identified 28 with BRCA mutations. A slightly increased relative risk of 1.79 was found for local recurrence in the BRCA carriers, although this difference was not statistically significant. More recently, Haffty et al94 reported long-term results (median follow-up, 12.7 years) of BCT in 105 patients with sporadic breast cancer compared to 22 patients with BRCA mutation–related breast cancers. Rate of ipsilateral breast cancer events was higher in the mutation carriers (49% v 21%; P = .001). However, the majority of these events were probably second primaries, based on the prolonged time to detection (median time, 8 years), location remote from the original primary tumor, and different histology from the primary tumor in the majority of cases. It is also notable that the incidence and locations of ipsilateral lesions were not consistent with neoplastic transformations related to scatter radiation. In a series reported by Pierce et al,95 73 BRCA mutation carriers undergoing lumpectomy and radiation therapy for early-stage breast cancer were matched to 219 women with presumed sporadic breast cancer who were also treated with BCT. With a median follow-up of approximately 5 years, there were no differences in the rates of local failure-free survival (96% for sporadic cancers v 99% for BRCA-associated cancers) or overall survival (91% for sporadic cancers v 86% for BRCA-associated cancers). No significant differences were seen in radiation toxicity either. An update of these findings with 10-year outcome was reported by Pierce et al96 at the 2003 San Antonio Breast Cancer Symposium. All of these studies (summarized in Table 2) have demonstrated similarly high rates of new contralateral breast cancers in patients with BRCA mutations, averaging four- to five-fold higher than the rates of new contralateral breast cancer seen in sporadic breast cancer cases. This increased incidence of contralateral disease represents further support for the impression that the high rates of developing new ipsilateral breast tumors after BCT are related to inherent risk in the breast tissue as opposed to radiation-induced transformations.
Expanded BCT Eligibility Neoadjuvant CTX and lumpectomy Preoperative chemotherapy (CTX) is standard management for patients with locally advanced breast cancer, resulting in primary tumor response rates of approximately 80%, and progression of disease in only 2% to 3%.52,103,104 This sequence allows for improved operability and provides an in vivo assessment of chemosensitivity. However, concerns that downsized tumors might leave a field of satellite nodules rather than shrink concentrically led to skepticism regarding BCT eligibility. This uncertainty motivated Singletary et al105 to conduct a feasibility study of BCT in 143 locally advanced breast cancer patients, all of whom received induction CTX. Meticulous pathology review of their mastectomy specimens revealed that 23% had been converted to BCT candidates by virtue of having residual unifocal tumors no larger than 4 cm and complete resolution of skin changes. Several randomized, prospective studies have now been completed (Table 3) which prove the oncologic safety of neoadjuvant CTX in early-stage as well as locally advanced breast cancer, with the concurrent demonstration that tumor downstaging does indeed improve eligibility for BCT without increasing local recurrence rates.106-116 A surgical component in the multidisciplinary care of these patients is essential, as the clinical assessment of complete response overestimates the pathologic findings by approximately three-fold, and local recurrence rates tend to be higher when radiation therapy is the only local therapy delivered after the neoadjuvant CTX.120
The NSABP B-18 trial114-116 randomly assigned more than 1,500 women with stages I to IIIA breast cancer to receive preoperative versus postoperative chemotherapy. This study demonstrated a statistically significant increase in BCT utilization for the preoperative CTX arm (68% v 60%). With a median follow-up of 72 months, the LR rates were 7.9% and 5.8% (no statistically significant difference) following BCT in the preoperative and postoperative chemotherapy arms, respectively. The conversion rate to BCT eligibility was greatest in the patients with T3 tumors at diagnosis. The NSABP also reported that local recurrence was somewhat higher in the subset of lumpectomy patients that were downstaged to become BCT-eligible in comparison to the BCT patients who were BCT candidates at presentation.115 However, this subset of downstaged BCT cases was predominantly made up of T3 tumors, and since LR is one manifestation of underlying tumor biology, it is not surprising that the more advanced-stage lesions would have higher local failure rates regardless of surgery type and treatment sequence. Also, radiation boost doses were not consistently used in the lumpectomy patients, and tamoxifen therapy was restricted to patients older than 50 years. Both of these interventions might have influenced local control in downstaged tumors. Lastly, the NSABP requires that only margin-negative lumpectomies be free of any tumor cells at the inked edge; a more aggressive approach to margin control might be necessary for lumpectomies in tumors that have been downsized by preoperative CTX. Induction CTX is a reasonable and safe treatment approach for patients with breast cancer of any stage if the clinician is certain that chemotherapy would be recommended in the postoperative setting. The risk of overtreatment can be minimized by obtaining multiple diagnostic core biopsy specimens to confirm that a lesion is predominantly invasive, as CTX is clearly inappropriate therapy for large-volume/palpable DCIS tumors or DCIS with microinvasion. Patients presenting with multiple tumors or extensive calcifications on initial mammogram should be counseled that preoperative CTX will not convert them to BCT eligibility, regardless of the extent of primary tumor shrinkage. Estimation of treatment response tends to be more challenging with invasive lobular cancers as well.121,122 If the tumor is not associated with any microcalcifications, then a radio-opaque clip should be inserted (preferably under ultrasound guidance) either prior to delivery of the neoadjuvant CTX or within the first couple of cycles. In the event that the patient has a complete clinical response to the preoperative CTX, this clip will serve as the target for subsequent mammography-assisted wire localization lumpectomy. Lesions associated with microcalcifications have an inherent localization target. Imaging with ultrasound and/or mammogram can be repeated after a couple of CTX cycles to evaluate tumor response. A decision may be made to switch the patient over to a non–cross-resistant chemotherapy regimen at this point if the tumor is failing to respond adequately. Alternative imaging modalities, such as CT,123,124 MRI,125-128 and PET129,130 scanning have also been proposed for monitoring CTX response. Inconsistent results have left physical examination, mammography, and ultrasound as the mainstay modalities for monitoring tumor response. Complete breast imaging should be repeated after all preoperative CTX cycles have been delivered, to facilitate final surgical planning. The mammogram should be studied for interval appearance of diffuse calcifications that may accumulate during treatment, or that may be unmasked as the primary tumor density responds to treatment. Plans for breast-preserving surgery may proceed if there was no evidence of multicentric disease at presentation and if the tumor is resectable by lumpectomy after the neoadjuvant treatment. BCT for subareolar tumors and Paget's disease Tumors involving the subareolar tissue and/or nipple (eg, Paget's disease of the nipple) have previously been considered relative contraindications to BCT because of the need for nipple removal. However, if disease appears to be confined to a central unifocal area, without diffuse microcalcifications, and if margin negativity can be achieved, then performing a central segmentectomy is a reasonable approach. The patient can undergo elective nipple-areolar reconstruction following completion of breast irradiation, if she so desires. The safety of the breast-sparing approach in Paget's disease has been reported by Pierce et al131 in a multicenter series of 30 patients revealing an 8-year disease-free survival of 95%. Lumpectomy for multiple breast tumors Early studies of lumpectomy for patients with multiple tumors revealed rates of local failure in excess of 20%, leading to this feature being widely considered to represent a contraindication to BCT.132-134 More recent studies, however, with closer attention to margin control, have demonstrated markedly improved outcome, as shown in Table 4. The generally accepted approach is that BCT can be attempted in these cases as long as the tumors can be encompassed within a single margin-negative lumpectomy specimen, and with a cosmetically acceptable volume of residual breast tissue.
Lumpectomy for LR after BCT A true local recurrence of breast cancer following prior lumpectomy and breast XRT would be characterized by location in the vicinity of the lumpectomy bed, and histology similar to the initial tumor. Second primary lesions are more likely to occur at peripheral sites remote from the initial cancer, frequently have a different microscopic pattern, and develop after a more prolonged interval. Numerous studies have shown that the true LR is a poor prognostic feature,139-141 especially if it is invasive rather than in situ, large,142-144 associated with skin involvement,142,145,146 or is detected after a short disease-free interval.140,147-149 Salvage mastectomy is currently standard-of-care for both in-breast recurrences and new ipsilateral primary breast cancers. The rationale for this approach is related to concerns regarding the biologic implications of a breast that continues to demonstrate tumorigenic potential, and to uncertainties about local management with minimal toxicity in a breast that has already received therapeutic chest wall irradiation. On the other hand, it can be reasonably argued that a repeat attempt at breast conservation may not necessarily threaten overall survival. Local recurrence is frequently viewed as an indicator of underlying tumor biology and not a source of metastatic disease. Improvements in breast imaging capable of detecting recurrence earlier, as well as more effective systemic therapies and innovative radiation delivery systems, may obviate the need for completion mastectomy if the breast can accommodate another lumpectomy. One of the earliest experiences with repeat lumpectomy in the setting of LR following prior lumpectomy and XRT was reported by Recht et al in 1989.150 In this study of 90 LR patients from the JCRT, one patient refused salvage mastectomy and was therefore managed with wide local excision followed by iridium implantation; she died disease free 6 years later. Since that time, several other investigators have reported their experiences with breast-sparing procedures (either with or without additional radiation therapy) in the management of recurrent cancer (Table 5). Advances in radiation delivery systems (intracavitary, brachytherapy, intensity-modulated radiation therapy, etc) have motivated Kuerer et al158 to propose a pilot multicenter clinical trial of BCT in women who experience an LR after prior lumpectomy and standard breast XRT.
Techniques for Optimizing Success With Lumpectomy and Margin Control Percutaneous diagnostic needle biopsy Approximately 50% of open, surgical diagnostic biopsies that reveal cancer have positive margins necessitating re-excision if the patient wishes BCT.159 The re-excision lumpectomy is likely to worsen the ultimate cosmetic result because of the larger volume of breast tissue resected. Percutaneous needle biopsies are increasingly being used to establish a diagnosis of breast cancer, and several studies160-162 have demonstrated that lumpectomies are more likely to be margin-negative when the breast cancer diagnosis has been established via percutaneous needle biopsy as opposed to open surgical diagnostic biopsy. Core needle biopsies are more accurate than fine needle aspirates, and have the advantage of providing adequate tissue for determining whether or not the lesion has an invasive histology. Core needle biopsies can be done freehand for palpable lesions, or they can be performed with stereotactic mammography or ultrasound guidance for nonpalpable lesions. Specimen handling and intraoperative margin assessment Direct communication between the surgeon and pathologist is the first step in optimizing margin control. At a minimum, the lumpectomy specimen should be oriented by the surgeon (when logistically feasible, this should be done in the presence of the pathologist), and the tissue margins should be inked (multiple-color inks may facilitate the orientation of the specimen margins). While frozen-section analysis of multiple margins is notoriously time consuming and inefficient, touch-prep evaluations are being increasingly advocated as a rapid and reliable alternative.86,163-166 The touch-prep method (also called imprint cytology) is relatively straight forward, and is based on the premise that cancer cells are more adherent to a glass surface than benign cells. The pathologist touches a microscope slide against the lumpectomy surface, fixes, and then stains the slide with hematoxylin and eosin. Several surfaces can be evaluated fairly quickly in this fashion, and reported results have been very favorable. Cox et al163 found an accuracy of 97.3% in use of touch-preps for margin analysis, and Klimberg et al164 estimated a margin assessment sensitivity at 100%. In a subsequent review of 701 lumpectomy specimens evaluated at the Moffitt Cancer Center (Tampa, FL), Cox et al165 reported a local recurrence rate of 2.7% for women whose lumpectomy margins were evaluated by touch-prep cytology, compared to 14.6% in referral cases whose margins were analyzed by conventional histopathology. A subset of 347 Moffitt Cancer Center cases had correlation between frozen section, touch-prep cytology, and permanent histopathology for margin analysis, revealing a false positive rate of 2.3% for touch preps and 0% frozen sections; false negatives occurred in 1.2% of touch preps compared to 5.5% of frozen sections. Other techniques that have been promoted in the effort to improve margin control with the initial lumpectomy have included recommendations to obtain shavings of the cavity margins for extended margin assessment,167 and performing mammograms of the lumpectomy specimen serial sections, as has been reported by Rubio et al168 for mastectomy specimens in cases of diffuse DCIS. For the latter strategy, the pathologist essentially sections the lumpectomy specimen "breadloaf" -style, and the specimens are aligned sequentially along the mammogram plate. The surgeon is then guided intraoperatively to cavity margins requiring wider excision by the demonstration of calcifications or tumor mass abutting any focal edge by mammography.
BCT is established as a safe oncologic treatment for breast cancer. A thorough understanding of risk factors for local recurrence and innovative maneuvers to achieve lumpectomy margin control is necessary for optimal application. Neoadjuvant CTX, as well as advances in breast imaging, cytopathology, and radiotherapy, have successfully expanded the number of lumpectomy-eligible cases.
The authors indicated no potential conflicts of interest.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
1. NIH consensus conference. Treatment of early-stage breast cancer. JAMA 265:391-395, 1991
2. 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
3. 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 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[CrossRef][Medline] 5. Van Dongen J, Bartelink H, Fentiman I: Factors influencing local relapse and survival and results of salvage treatment after breast-conserving therapy in operable breast cancer: EORTC trial 10801, breast conservation compared with mastectomy in TNM stage I and II breast cancer. Eur J Cancer 28A:801-805, 1992
6. 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 7. Sarrazin D, Le MG, Arriagada R, et al: Ten-year results of a randomized trial comparing a conservative treatment to mastectomy in early breast cancer. Radiother Oncol 14:177-184, 1989[CrossRef][Medline] 8. Blichert-Toft M, Rose CA, Anderson J: 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 11:19-25, 1992
9. Voogd AC, 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 10. Morris AD, Morris RD, Wilson JF, et al: Breast-conserving therapy vs mastectomy in early-stage breast cancer: A meta-analysis of 10-year survival. Cancer J Sci Am 3:6-12, 1997[Medline]
11. Morrow M, White J, Moughan J, et al: Factors predicting the use of breast-conserving therapy in stage I and II breast carcinoma. J Clin Oncol 19:2254-2262, 2001 12. Locker G, Sainsbury R, Cuzick J: The ATAC Trialists' Group. Breast surgery in the ATAC trial: Women from the United States are more likely to have mastectomy, San Antonio Breast Cancer Symposium. San Antonio, Texas, 2002 13. Swanson GM, Satariano ER, Satariano WA, et al: Trends in conserving treatment of invasive carcinoma of the breast in females. Surg Gynecol Obstet 171:465-471, 1990[Medline] 14. Samet JM, Hunt WC, Farrow DC: Determinants of receiving breast-conserving surgery. The Surveillance, Epidemiology, and End Results Program, 1983-1986. Cancer 73:2344-2351, 1994[CrossRef][Medline]
15. Johantgen ME, Coffey RM, Harris DR, et al: Treating early-stage breast cancer: Hospital characteristics associated with breast-conserving surgery. Am J Public Health 85:1432-1434, 1995 16. Ayanian JZ, Guadagnoli E: Variations in breast cancer treatment by patient and provider characteristics. Breast Cancer Res Treat 40:65-74, 1996[CrossRef][Medline] 17. Nattinger AB, Gottlieb MS, Veum J, et al: Geographic variation in the use of breast-conserving treatment for breast cancer. N Engl J Med 326:1102-1107, 1992[Abstract] 18. Lucci A, Shoher A, Sherman M, et al: Assessment of the current Medicare reimbursement system for breast cancer operations. Society of Surgical Oncology Annual Cancer Symposium, New York, NY, 2004, p S75 (abstr 84) 19. Holli K, Saaristo R, Isola J, et al: Lumpectomy with or without postoperative radiotherapy for breast cancer with favorable prognostic features: Results of a randomized study. Br J Cancer 84:164-169, 2001[CrossRef][Medline]
20. Clark R, Whelan T, Levine M, et al: Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: An update. J Natl Cancer Inst 88:1659-1664, 1996 21. Forrest A, Stewart H, Everington D, et al: Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet 348:708-713, 1996[CrossRef][Medline] 22. Inoue M, Tanaka H, Masuda R, et al: Local control and cosmetic outcome after sector resection with or without radiation therapy for early breast cancer. Breast Cancer 3:39-46, 1996[Medline]
23. 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
24. 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
25. 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
26. Morrow M, Strom EA, Bassett LW, et al: Standard for breast conservation therapy in the management of invasive breast carcinoma. CA Cancer J Clin 52:277-300, 2002 27. Brekelmans CT, Voogd AC, Botke G, et al: Family history of breast cancer and local recurrence after breast-conserving therapy. The Dutch Study Group on Local Recurrence after Breast Conservation (BORST). Eur J Cancer 35:620-626, 1999 28. Chabner E, Nixon A, Gelman R, et al: Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer. J Clin Oncol 16:2045-2051, 1998[Abstract]
29. Vlastos G, Mirza NQ, Meric F, et al: Breast-conservation therapy in early-stage breast cancer patients with a positive family history. Ann Surg Oncol 9:912-919, 2002 30. Voogd AC, Peterse JL, Crommelin MA, et al: Histological determinants for different types of local recurrence after breast-conserving therapy of invasive breast cancer. Dutch Study Group on local Recurrence after Breast Conservation (BORST). Eur J Cancer 35:1828-1837, 1999 31. Salvadori B, Biganzoli E, Veronesi P, et al: Conservative surgery for infiltrating lobular breast carcinoma. Br J Surg 84:106-109, 1997[CrossRef][Medline] 32. Elkhuizen PH, Voogd AC, van den Broek LC, et al: Risk factors for local recurrence after breast-conserving therapy for invasive carcinomas: A case-control study of histological factors and alterations in oncogene expression. Int J Radiat Oncol Biol Phys 45:73-83, 1999[CrossRef][Medline] 33. Wazer DE, Schmidt-Ullrich RK, Ruthazer R, et al: Factors determining outcome for breast-conserving irradiation with margin-directed dose escalation to the tumor bed. Int J Radiat Oncol Biol Phys 40:851-858, 1998[CrossRef][Medline] 34. Holland PA, Shah A, Howell A, et al: Lobular carcinoma of the breast can be managed by breast-conserving therapy. Br J Surg 82:1364-1366, 1995[Medline] 35. Schnitt SJ, Connolly JL, Recht A, et al: Influence of infiltrating lobular histology on local tumor control in breast cancer patients treated with conservative surgery and radiotherapy. Cancer 64:448-454, 1989[CrossRef][Medline] 36. Abner AL, Connolly JL, Recht A, et al: The relation between the presence and extent of lobular carcinoma in situ and the risk of local recurrence for patients with infiltrating carcinoma of the breast treated with conservative surgery and radiation therapy. Cancer 88:1072-1077, 2000[CrossRef][Medline] 37. Carolin KA, Tekyi-Mensah S, Pass HA: Lobular carcinoma in situ and invasive cancer: The contralateral breast controversy. Breast J 8:263-268, 2002[CrossRef][Medline] 38. Moran M, Haffty BG: Lobular carcinoma in situ as a component of breast cancer: The long-term outcome in patients treated with breast-conservation therapy. Int J Radiat Oncol Biol Phys 40:353-358, 1998[CrossRef][Medline] 39. Hussien M, Lioe T, Finnegan J, et al: Surgical treatment for invasive lobular carcinoma of the breast. Breast 12:23-35, 2003[CrossRef][Medline] 40. Sasson AR, Fowble B, Hanlon AL, et al: Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation. Cancer 91:1862-1869, 2001[CrossRef][Medline] 41. Winchester DP, Cox JD: Standards for diagnosis and management of invasive breast carcinoma: American College of Radiology, American College of Surgeons, College of American Pathologists. Society of Surgical Oncology. CA Cancer J Clin 48:83-107, 1998[Abstract] 42. Veronesi U, Salvadori B, Luini A, et al: Breast conservation is a safe method in patients with small cancer of the breast. Long-term results of three randomised trials on 1,973 patients. Eur J Cancer 31A:1574-1579, 1995
43. Spivack B, Khanna MM, Tafra L, et al: Margin status and local recurrence after breast-conserving surgery. Arch Surg 129:952-957, 1994 44. Noguchi S, Koyama H, Kasugai T, et al: A case-control study on risk factors for local recurrences or distant metastases in breast cancer patients treated with breast-conserving surgery. Oncology 54:468-474, 1997[Medline] 45. Slotman BJ, Meyer OW, Njo KH, et al: Importance of timing of radiotherapy in breast conserving treatment for early stage breast cancer. Radiother Oncol 30:206-212, 1994[CrossRef][Medline] 46. Borger J, Kemperman H, Hart A, et al: Risk factors in breast-conservation therapy. J Clin Oncol 12:653-660, 1994[Abstract] 47. Burke MF, Allison R, Tripcony L: Conservative therapy of breast cancer in Queensland. Int J Radiat Oncol Biol Phys 31:295-303, 1995[CrossRef][Medline] 48. Heimann R, Powers C, Halpem HJ, et al: Breast preservation in stage I and II carcinoma of the breast. The University of Chicago experience. Cancer 78:1722-1730, 1996[CrossRef][Medline] 49. Dewar JA, Arriagada R, Benhamou S, et al: Local relapse and contralateral tumor rates in patients with breast cancer treated with conservative surgery and radiotherapy (Institut Gustave Roussy 1970-1982). IGR Breast Cancer Group. Cancer 76:2260-2265, 1995[CrossRef][Medline] 50. Mansfield CM, Komarnicky LT, Schwartz GF, et al: Ten-year results in 1070 patients with stages I and II breast cancer treated by conservative surgery and radiation therapy. Cancer 75:2328-2336, 1995[CrossRef][Medline] 51. Leong C, Boyages J, Jayasinghe UW, et al: Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node-negative breast carcinoma. Cancer 100:1823-1832, 2004[CrossRef][Medline] 52. Newman LA, Washington TA: New trends in breast conservation therapy. Surg Clin North Am 83:841-883, 2003[CrossRef][Medline] 53. Singletary SE: Surgical margins in patients with early-stage breast cancer treated with breast conservation therapy. Am J Surg 184:383-393, 2002[CrossRef][Medline] 54. Veronesi U: How important is the assessment of resection margins in conservative surgery for breast cancer? Cancer 74:1660-1661, 1994[CrossRef][Medline] 55. Veronesi U, Luini A, Galimberti V, et al: Conservation approaches for the management of stage I/II carcinoma of the breast: Milan Cancer Institute trials. World J Surg 18:70-75, 1994[CrossRef][Medline] 56. Veronesi U, Volterrani F, Luini A, et al: Quadrantectomy versus lumpectomy for small size breast cancer. Eur J Cancer 26:671-673, 1990
57. Ryoo MC, Kagan AR, Wollin M, et al: Prognostic factors for recurrence and cosmesis in 393 patients after radiation therapy for early mammary carcinoma. Radiology 172:555-559, 1989 58. Touboul E, Buffat L, Belkacemi Y, et al: Local recurrences and distant metastases after breast-conserving surgery and radiation therapy for early breast cancer. Int J Radiat Oncol Biol Phys 43:25-38, 1999[CrossRef][Medline] 59. DiBiase SJ, Komarnicky LT, Schwartz GF, et al: The number of positive margins influences the outcome of women treated with breast preservation for early stage breast carcinoma. Cancer 82:2212-2220, 1998[CrossRef][Medline] 60. Freedman G, Fowble B, Hanlon A, et al: Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy. Int J Radiat Oncol Biol Phys 44:1005-1015, 1999[CrossRef][Medline] 61. Gould EW, Robinson PG: The pathologist's examination of the "lumpectomy"—the pathologists' view of surgical margins. Semin Surg Oncol 8:129-135, 1992[Medline] 62. Schnitt SJ, Connolly JL, Harris JR, et al: Pathologic predictors of early local recurrence in stage I and II breast cancer treated by primary radiation therapy. Cancer 53:1049-1057, 1984[CrossRef][Medline]
63. 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 64. Gage I, Schnitt SJ, Nixon AJ, et al: Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy. Cancer 78:1921-1928, 1996[CrossRef][Medline] 65. Leborgne F, Leborgne JH, Ortega B, et al: Breast conservation treatment of early stage breast cancer: Patterns of failure. Int J Radiat Oncol Biol Phys 31:765-775, 1995[CrossRef][Medline] 66. Boyages J, Recht A, Connolly JL, et al: Early breast cancer: Predictors of breast recurrence for patients treated with conservative surgery and radiation therapy. Radiother Oncol 19:29-41, 1990[CrossRef][Medline] 67. 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 74:1746-1751, 1994[CrossRef][Medline] 68. Anscher MS, Jones P, Prosnitz LR, et al: Local failure and margin status in early-stage breast carcinoma treated with conservation surgery and radiation therapy. Ann Surg 218:22-28, 1993[Medline] 69. Smitt MC, Nowels KW, Zdeblick MJ, et al: The importance of the lumpectomy surgical margin status in long-term results of breast conservation. Cancer 76:259-267, 1995[CrossRef][Medline]
70. Mirza NQ, Vlastos G, Meric F, et al: Predictors of locoregional recurrence among patients with early-stage breast cancer treated with breast-conserving therapy. Ann Surg Oncol 9:256-265, 2002 71. Dalberg K, Mattsson A, Rutqvist LE, et al: Breast conserving surgery for invasive breast cancer: Risk factors for ipsilateral breast tumor recurrences. Breast Cancer Res Treat 43:73-86, 1997[CrossRef][Medline]
72. Arriagada R, Le MG, Guinebretiere JM, et al: Late local recurrences in a randomised trial comparing conservative treatment with total mastectomy in early breast cancer patients. Ann Oncol 14:1617-1622, 2003 73. Jobsen JJ, van der Palen J, Ong F, et al: The value of a positive margin for invasive carcinoma in breast-conservative treatment in relation to local recurrence is limited to young women only. Int J Radiat Oncol Biol Phys 57:724-731, 2003[CrossRef][Medline]
74. Orel SG, Schnall MD: MR imaging of the breast for the detection, diagnosis, and staging of breast cancer. Radiology 220:13-30, 2001 75. Morris EA: Review of breast MRI: Indications and limitations. Semin Roentgenol 36:226-237, 2001[CrossRef][Medline] 76. Chen C, Orel SG, Harris E, et al: Outcome after treatment of patients with mammographically occult, magnetic resonance imaging-detected breast cancer presenting with axillary lymphadenopathy. Clin Breast Cancer 5:72-77, 2004[Medline] 77. Baker DR: Magnetic resonance imaging of occult breast cancer. Clin Breast Cancer 1:66-67, 2000[Medline] 78. Olson JA, Jr., Morris EA, Van Zee KJ, et al: Magnetic resonance imaging facilitates breast conservation for occult breast cancer. Ann Surg Oncol 7:411-415, 2000[Abstract] 79. Davis PL, Julian TB, Staiger M, et al: Magnetic resonance imaging detection and wire localization of an ‘occult’ breast cancer. Breast Cancer Res Treat 32:327-330, 1994[CrossRef][Medline] 80. Tan JE, Orel SG, Schnall MD, et al: Role of magnetic resonance imaging and magnetic resonance imaging–guided surgery in the evaluation of patients with early-stage breast cancer for breast conservation treatment. Am J Clin Oncol 22:414-418, 1999[CrossRef][Medline]
81. Fischer U, Kopka L, Grabbe E: Breast carcinoma: Effect of preoperative contrast-enhanced MR imaging on the therapeutic approach. Radiology 213:881-888, 1999
82. Lee JM, Orel SG, Czerniecki BJ, et al: MRI before reexcision surgery in patients with breast cancer. AJR Am J Roentgenol 182:473-480, 2004
83. Rodenko GN, Harms SE, Pruneda JM, et al: MR imaging in the management before surgery of lobular carcinoma of the breast: Correlation with pathology. AJR Am J Roentgenol 167:1415-1419, 1996 84. Schelfout K, Van Goethem M, Kersschot E, et al: Preoperative breast MRI in patients with invasive lobular breast cancer. Eur Radiol 14:1209-1216, 2004[Medline] 85. Uematsu T, Sano M, Homma K, et al: Value of three-dimensional helical CT image-guided planning for made-to-order lumpectomy in breast cancer patients. Breast J 10:33-37, 2004[CrossRef][Medline] 86. Henry-Tillman R, Johnson A, Smith L, et al: Intraoperative ultrasound and other techniques to achieve negative margins. Semin Surg Oncol 20:206-213, 2001[CrossRef][Medline] 87. Rahusen FD, Bremers AJ, Fabry HF, et al: Ultrasound-guided lumpectomy of nonpalpable breast cancer versus wire-guided resection: A randomized clinical trial. Ann Surg Oncol 4:994-998, 2002
88. Berg WA, Gilbreath PL: Multicentric and multifocal cancer: Whole-breast US in preoperative evaluation. Radiology 214:59-66, 2000
89. Moon WK, Noh DY, Im JG: Multifocal, multicentric, and contralateral breast cancers: Bilateral whole-breast US in the preoperative evaluation of patients. Radiology 224:569-576, 2002 90. Malur S, Wurdinger S, Moritz A, et al: Comparison of written reports of mammography, sonography and magnetic resonance mammography for preoperative evaluation of breast lesions, with special emphasis on magnetic resonance mammography. Breast Cancer Res 3:55-60, 2001[CrossRef][Medline] 91. Hata T, Takahashi H, Watanabe K, et al: Magnetic resonance imaging for preoperative evaluation of breast cancer: A comparative study with mammography and ultrasonography. J Am Coll Surg 198:190-197, 2004[CrossRef][Medline] 92. Morrow M: Magnetic resonance imaging in the preoperative evaluation of breast cancer: Primum non nocere. J Am Coll Surg 198:240-241, 2004[CrossRef][Medline]
93. Robson M, Levin D, Federici M, et al: Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 91:2112-2117, 1999 94. Haffty BG, Harrold E, Khan AJ, et al: Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471-1477, 2002[CrossRef][Medline]
95. Pierce LJ, Strawderman M, Narod SA, et al: Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 18:3360-3369, 2000 96. Pierce L, Levin A: T R, et al: Ten-year outcome of breast-conserving surgery (BCS) and radiotherapy (RT) in women with breast cancer (BC) and germline BRCA 1/2 mutations: Results from an international collaboration. San Antonio Breast Cancer Symposium, San Antonio, TX, 2003 (abstr 5) 97. Verhoog LC, Brekelmans CT, Seynaeve C, et al: Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 351:316-321, 1998[CrossRef][Medline] 98. Eccles D, Simmonds P, Goddard J, et al: Familial breast cancer: An investigation into the outcome of treatment for early stage disease. Fam Cancer 1:65-72, 2001[CrossRef][Medline] 99. Delaloge S, Kloos I, Ariane D, et al: Young age is the major predictor of local relapse among conservatively treated BRCA1- BRCA2- or non-BRCA-linked hereditary breast cancer. Proc Am Soc Clin Oncol 22:11, 2003 (abstr 41)
100. El-Tamer M, Russo D, Troxel A, et al: Survival and recurrence after breast cancer in BRCA1/2 mutation carriers. Ann Surg Oncol 11:157-164, 2004 101. Seynaeve C, Verhoog LC, van de Bosch LM, et al: Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy. Eur J Cancer 40:1150-1158, 2004 102. Robson ME, Chappuis PO, Satagopan J, et al: A combined analysis of outcome following breast cancer: Differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 6:R8-R17, 2004[CrossRef][Medline] 103. Hunt KK, Ames FC, Singletary SE, et al: Locally advanced noninflammatory breast cancer. Surg Clin North Am 76:393-410, 1996[CrossRef][Medline] 104. Newman LA: Management of patients with locally advanced breast cancer. Curr Oncol Rep 6:53-61, 2004[Medline] 105. Singletary SE, McNeese MD, Hortobagyi GN: Feasibility of breast-conservation surgery after induction chemotherapy for locally advanced breast carcinoma. Cancer 69:2849-2852, 1992[CrossRef][Medline]
106. Mauriac L, Durand M, Avril A, et al: Effects of primary chemotherapy in conservative treatment of breast cancer patients with operable tumors larger than 3 cm. Results of a randomized trial in a single centre. Ann Oncol 2:347-354, 1991
107. Mauriac L, MacGrogan G, Avril A, et al: Neoadjuvant chemotherapy for operable breast carcinoma larger than 3 cm: A unicentre randomized trial with a 124-month median follow-up. Institut Bergonie Bordeaux Groupe Sein (IBBGS). Ann Oncol 10:47-52, 1999 108. Scholl SM, Asselain B, Palangie T, et al: Neoadjuvant chemotherapy in operable breast cancer. Eur J Cancer 27:1668-1671, 1991 109. Scholl SM, Fourquet A, Asselain B, et al: Neoadjuvant versus adjuvant chemotherapy in premenopausal patients with tumours considered too large for breast conserving surgery: Preliminary results of a randomised trial: S6. Eur J Cancer 30A:645-652, 1994 110. Scholl SM, Pierga JY, Asselain B, et al: Breast tumour response to primary chemotherapy predicts local and distant control as well as survival. Eur J Cancer 31A:1969-1975, 1995
111. Powles TJ, Hickish TF, Makris A, et al: Randomized trial of chemoendocrine therapy started before or after surgery for treatment of primary breast cancer. J Clin Oncol 13:547-552, 1995
112. Makris A, Powles TJ, Ashley SE, et al: A reduction in the requirements for mastectomy in a randomized trial of neoadjuvant chemoendocrine therapy in primary breast cancer. Ann Oncol 9:1179-1184, 1998 113. Makris A, Powles TJ, Dowsett M, et al: Prediction of response to neoadjuvant chemoendocrine therapy in primary breast carcinomas. Clin Cancer Res 3:593-600, 1997[Abstract]
114. Fisher B, Brown A, Mamounas E, et al: Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: Findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol 15:2483-2493, 1997 115. 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] 116. 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:96-102, 2001
117. van der Hage JA, van de Velde CJ, Julien JP, et al: Preoperative chemotherapy in primary operable breast cancer: Results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol 19:4224-4237, 2001 118. Gianni L, Baselga J, Eiermann W, et al: First report of the European Cooperative Trial in Operable Breast Cancer (ECTO): Effects of primary systemic therapy (PST) on local-regional disease. Proc Am Soc Clin Oncol 21:2002 (abstr 132) 119. Jakesz R, Group ABCCS: Comparison of pre- vs. postoperative chemotherapy in breast cancer patients: Four-year results of Austrian Breast and Colorectal Study Group (ABCSG) Trial 7. Proc Am Soc Clin Oncol 20:2001 (abstr 125)
120. Ring A, Webb A, Ashley S, et al: Is surgery necessary after complete clinical remission following neoadjuvant chemotherapy for early breast cancer? J Clin Oncol 21:4540-4545, 2003
121. Newman LA, Buzdar AU, Singletary SE, et al: A prospective trial of preoperative chemotherapy in resectable breast cancer: Predictors of breast-conservation therapy feasibility. Ann Surg Oncol 9:228-234, 2002 122. Mathieu MC, Rouzier R, Llombart-Cussac A, et al: The poor responsiveness of infiltrating lobular breast carcinomas to neoadjuvant chemotherapy can be explained by their biological profile. Eur J Cancer 40:342-351, 2004 123. Akashi-Tanaka S, Fukutomi T, Sato N, et al: The use of contrast-enhanced computed tomography before neoadjuvant chemotherapy to identify patients likely to be treated safely with breast-conserving surgery. Ann Surg 239:238-243, 2004[CrossRef][Medline] 124. Akashi-Tanaka S, Fukutomi T, Sato N, et al: The role of computed tomography in the selection of breast cancer treatment. Breast Cancer 10:198-203, 2003[Medline]
125. Rosen EL, Blackwell KL, Baker JA, et al: Accuracy of MRI in the detection of residual breast cancer after neoadjuvant chemotherapy. AJR Am J Roentgenol 181:1275-1282, 2003 126. Warren RM, Bobrow LG, Earl HM, et al: Can breast MRI help in the management of women with breast cancer treated by neoadjuvant chemotherapy? Br J Cancer 90:1349-1360, 2004[CrossRef][Medline] 127. Martincich L, Montemurro F, De Rosa G, et al: Monitoring response to primary chemotherapy in breast cancer using dynamic contrast-enhanced magnetic resonance imaging. Breast Cancer Res Treat 83:67-76, 2004[CrossRef][Medline] 128. Londero V, Bazzocchi M, Del Frate C, et al: Locally advanced breast cancer: comparison of mammography, sonography and MR imaging in evaluation of residual disease in women receiving neoadjuvant chemotherapy. Eur Radiol 14:1371-1379, 2004[Medline] 129. Burcombe RJ, Makris A, Pittam M, et al: Evaluation of good clinical response to neoadjuvant chemotherapy in primary breast cancer using [18F]-fluorodeoxyglucose positron emission tomography. Eur J Cancer 38:375-379, 2002 130. Nakamura S, Kenjo H, Nishio T, et al: 3D-MR mammography-guided breast conserving surgery after neoadjuvant chemotherapy: Clinical results and future perspectives with reference to FDG-PET. Breast Cancer 8:351-354, 2001[Medline] 131. Pierce LJ, Haffty BG, Solin LJ, et al: The conservative management of Paget's disease of the breast with radiotherapy. Cancer 80:1065-1072, 1997[CrossRef][Medline] 132. Kurtz JM, Jacquemier J, Amalric R, et al: Breast-conserving therapy for macroscopically multiple cancers. Ann Surg 212:38-44, 1990[Medline] 133. Leopold KA, Recht A, Schnitt SJ, et al: Results of conservative surgery and radiation therapy for multiple synchronous cancers of one breast. Int J Radiat Oncol Biol Phys 16:11-16, 1989[Medline] 134. Wilson LD, Beinfield M, McKhann CF, et al: Conservative surgery and radiation in the treatment of synchronous ipsilateral breast cancers. Cancer 72:137-142, 1993[CrossRef][Medline] 135. Hartsell WF, Recine DC, Griem KL, et al: Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy? Int J Radiat Oncol Biol Phys 30:49-53, 1994[Medline] 136. Cho LC, Senzer N, Peters GN: Conservative surgery and radiation therapy for macroscopically multiple ipsilateral invasive breast cancers. Am J Surg 183:650-654, 2002[CrossRef][Medline] 137. Kaplan J, Giron G, Tartter PI, et al: Breast conservation in patients with multiple ipsilateral synchronous cancers. J Am Coll Surg 197:726-729, 2003[CrossRef][Medline] 138. Okumura S, Mitsumori M, Yamauchi C, et al: Feasibility of breast-conserving therapy for macroscopically multiple ipsilateral breast cancer. Int J Radiat Oncol Biol Phys 59:146-151, 2004[CrossRef][Medline] 139. Fisher B, Anderson S, Fisher ER, et al: Significance of ipsilateral breast tumour recurrence after lumpectomy. Lancet 338:327-331, 1991[CrossRef][Medline]
140. Veronesi U, Marubini E, Del Vecchio M, et al: Local recurrences and distant metastases after conservative breast cancer treatments: Partly independent events. J Natl Cancer Inst 87:19-27, 1995 141. Fredriksson I, Liljegren G, Arnesson LG, et al: Local recurrence in the breast after conservative surgery—a study of prognosis and prognostic factors in 391 women. Eur J Cancer 38:1860-1870, 2002 142. Voogd AC, van Tienhoven G, Peterse HL, et al: Local recurrence after breast conservation therapy for early stage breast carcinoma: Detection, treatment, and outcome in 266 patients. Dutch Study Group on Local Recurrence after Breast Conservation (BORST). Cancer 85:437-446, 1999[CrossRef][Medline] 143. Cajucom CC, Tsangaris TN, Nemoto T, et al: Results of salvage mastectomy for local recurrence after breast-conserving surgery without radiation therapy. Cancer 71:1774-1779, 1993[CrossRef][Medline] 144. Haffty BG, Fischer D, Beinfield M, et al: Prognosis following local recurrence in the conservatively treated breast cancer patient. Int J Radiat Oncol Biol Phys 21:293-298, 1991[Medline] 145. Gage I, Schnitt SJ, Recht A, et al: Skin recurrences after breast-conserving therapy for early-stage breast cancer. J Clin Oncol 16:480-486, 1998[Abstract] 146. Clarke DH, Le MG, Sarrazin D, et al: Analysis of local-regional relapses in patients with early breast cancers treated by excision and radiotherapy: Experience of the Institut Gustave-Roussy. Int J Radiat Oncol Biol Phys 11:137-145, 1985[Medline] 147. Whelan T, Clark R, Roberts R, et al: Ipsilateral breast tumor recurrence postlumpectomy is predictive of subsequent mortality: Results from a randomized trial. Investigators of the Ontario Clinical Oncology Group. Int J Radiat Oncol Biol Phys 30:11-16, 1994[Medline] 148. Doyle T, Schultz DJ, Peters C, et al: Long-term results of local recurrence after breast conservation treatment for invasive breast cancer. Int J Radiat Oncol Biol Phys 51:74-80, 2001[Medline] 149. Haffty BG, Reiss M, Beinfield M, et al: Ipsilateral breast tumor recurrence as a predictor of distant disease: Implications for systemic therapy at the time of local relapse. J Clin Oncol 14:52-57, 1996[Abstract] 150. Recht A, Schnitt SJ, Connolly JL, et al: Prognosis following local or regional recurrence after conservative surgery and radiotherapy for early stage breast carcinoma. Int J Radiat Oncol Biol Phys 16:3-9, 1989[Medline] 151. Kurtz JM, Jacquemier J, Amalric R, et al: Is breast conservation after local recurrence feasible? Eur J Cancer 27:240-244, 1991 152. Abner AL, Recht A, Eberlein T, et al: Prognosis following salvage mastectomy for recurrence in the breast after conservative surgery and radiation therapy for early-stage breast cancer. J Clin Oncol 11:44-48, 1993[Abstract] 153. Maulard C, Housset M, Brunel P, et al: Use of perioperative or split-course interstitial brachytherapy techniques for salvage irradiation of isolated local recurrences after conservative management of breast cancer. Am J Clin Oncol 18:348-352, 1995[Medline] 154. Dalberg K, Mattsson A, Sandelin K, et al: Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer. Breast Cancer Res Treat 49:69-78, 1998[CrossRef][Medline] 155. Salvadori B, Marubini E, Miceli R, et al: Reoperation for locally recurrent breast cancer in patients previously treated with conservative surgery. Br J Surg 86:84-87, 1999[CrossRef][Medline] 156. Deutsch M: Repeat high-dose external beam irradiation for in-breast tumor recurrence after previous lumpectomy and whole breast irradiation. Int J Radiat Oncol Biol Phys 53:687-691, 2002[CrossRef][Medline]
157. Resch A, Fellner C, Mock U, et al: Locally recurrent breast cancer: pulse dose rate brachytherapy for repeat irradiation following lumpectomy—a second chance to preserve the breast. Radiology 225:713-718, 2002 158. Kuerer HM, Arthur DW, Haffty BG: Repeat breast-conserving surgery for in-breast local breast carcinoma recurrence. Cancer 100:2269-2280, 2004[CrossRef][Medline] 159. Cox CE, Reintgen DS, Nicosia SV, et al: Analysis of residual cancer after diagnostic breast biopsy: An argument for fine-needle aspiration cytology. Ann Surg Oncol 2:201-206, 1995[Abstract] 160. Staradub VL, Rademaker AW, Morrow M: Factors influencing outcomes for breast conservation therapy of mammographically detected malignancies. J Am Coll Surg 196:518-524, 2003[CrossRef][Medline]
161. Liberman L, Goodstine SL, Dershaw DD, et al: One operation after percutaneous diagnosis of nonpalpable breast cancer: Frequency and associated factors. AJR Am J Roentgenol 178:673-679, 2002 162. Tartter PI, Bleiweiss IJ, Levchenko S: Factors associated with clear biopsy margins and clear reexcision margins in breast cancer specimens from candidates for breast conservation. J Am Coll Surg 185:268-273, 1997[CrossRef][Medline] 163. Luu HH, Otis CN, Reed WP, Jr., et al: The unsatisfactory margin in breast cancer surgery. Am J Surg 178:362-366, 1999[CrossRef][Medline]
164. Cox CE, Ku NN, Reintgen DS, et al: Touch preparation cytology of breast lumpectomy margins with histologic correlation. Arch Surg 126:490-493, 1991 165. Klimberg VS, Westbrook KC, Korourian S: Use of touch preps for diagnosis and evaluation of surgical margins in breast cancer. Ann Surg Oncol 5:220-226, 1998[Abstract] 166. Cox CE, Pendas S, Ku NN, et al: Local recurrence of breast cancer after cytological evaluation of lumpectomy margins. Am Surg 64:533-538, 1998[Medline] 167. Klimberg VS, Harms S, Korourian S: Assessing margin status. Surg Oncol 8:77-84, 1999[CrossRef][Medline] 168. Barthelmes L, Al Awa A, Crawford DJ: Effect of cavity margin shavings to ensure completeness of excision on local recurrence rates following breast conserving surgery. Eur J Surg Oncol 29:644-648, 2003[CrossRef][Medline] 169. Rubio IT, Mirza N, Sahin AA, et al: Role of specimen radiography in patients treated with skin-sparing mastectomy for ductal carcinoma in situ of the breast. Ann Surg Oncol 7:544-548, 2000[Abstract] Submitted September 10, 2004; accepted November 29, 2004.
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