Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique

OBJECTIVE: The effect of the type of biopsy (needle vs. excisional) on lumpectomy margin status has not been well established. The objective of this study was to determine whether needle biopsy is associated with a higher positive margin rate at time of lumpectomy. METHODS: We evaluated this hypothesis in the setting of a prospective multi-institutional study. A total of 3975 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study from May 7, 1998 to June 3, 2003. Patients who underwent lumpectomy at the time of their sentinel lymph node biopsy were the focus of this analysis. Patients with clinical stage T1 N0 and T2 N0breast cancer were eligible; 29 patients were found to have T3 tumors on final pathology. Pathologists at each institution defined margin positivity, and tumor at the inked margin of resection was the study guideline. RESULTS: Median patient age was 59 years, and median tumor size was 1.5 cm. A total of 2658 patients underwent lumpectomy with the following results. The cancer of 1515 patients was diagnosed by fine-needle or core-needle biopsy and of 821 patients was diagnosed by excisional biopsy; in 322 patients the method of diagnosis was unknown. The type of previous biopsy did not significantly affect the positive-margin rate at the time of lumpectomy (13.3% vs. 11.0% for needle and excisional biopsy, respectively, P = 0.107). However, patients with larger tumors were more often found to have a positive margin (11.4% vs. 13.9% vs. 27.6% for T1, T2, and T3 tumors, respectively; P = 0.010). No difference was found in margin status after excision of palpable versus nonpalpable tumors (10.6% vs. 10.9%, respectively, P = 0.743). Histologic subtype, however, did affect margin status (15.8% vs. 9.8% positive margins for lobular vs. ductal type, respectively, P = 0.003). CONCLUSIONS: In this multi-institutional study, increasing tumor size and lobular histologic subtype were associated with a greater likelihood of a positive margin. The type of biopsy, needle or excisional, had no effect on the ability to achieve negative margins.     

A comparison of ink-directed and traditional whole-cavity re-excision for breast lumpectomy specimens with positive margins

Background: Excising a breast tumor with negative margins minimizes local recurrence. With a positive margin, the standard re-excision consists of excising the whole cavity and all surrounding breast tissue. By marking the sides of the lumpectomy specimen with six different colored inks, the surgeon can limit the re-excision to the involved margin. We compared the local recurrence rate after these two re-excision methods.Methods: Records were reviewed of 527 women (546 breasts) treated with lumpectomy at two institutions. The log-rank test was used to compare the local recurrence–free survival.Results: Of 546 tumors, 245 (45%) had negative margins on the initial lumpectomy and were not re-excised. Fifty-five percent had a positive or close margin; 181 underwent whole-cavity re-excision, and 120 had ink-directed re-excision. The mean follow-up time was 3.4 years. There was no significant difference in local recurrence for the patients whose initial margin was negative (3.7%) compared with the 243 patients with initially positive margins who underwent a re-excision (3.3%). Eleven of 181 (6%) patients undergoing a whole-cavity re-excision developed a local recurrence, compared with none of 120 (0%) patients with an ink-directed re-excision (P = not significant). Tissue mass excised was significantly smaller in the ink-directed group (23 vs. 83 g, P < .05).Conclusions: Ink-directed re-excision of lumpectomy specimens with positive margins minimizes the amount of breast tissue removed without increasing the incidence of local recurrence and is therefore preferable to the standard whole-cavity method.     

The influence of additional surgical margins on the total specimen volume excised and the reoperative rate after breast-conserving surgery

BACKGROUND: It is unclear whether the additional removal of breast tissue during breast-conserving therapy (BCT) for breast cancer beyond the standard lumpectomy reduces the incidence of inadequate microscopic margins found at pathological examination and subsequent reoperation. This study compares the reoperative rates after initial BCT in 3 groups of patients who underwent lumpectomy with complete resection of 4 to 6 additional margins, lumpectomy with selective resection of 1 to 3 additional margins, or standard lumpectomy. METHODS: Retrospective data were reviewed from 171 selected cases of BCT, from May 2000 to February 2006. Forty-five cases involved lumpectomy with complete resection of 4 to 6 additional margins; 77 involved lumpectomy with selective resection of 1 to 3 additional margins, whereas 49 involved standard lumpectomy. All samples underwent pathologic analysis of inked resection margins by permanent section. The 3 groups were compared for patient demographics, tumor size and histologic subtype, tumor stage, margin status, excised specimen volume, and eventual subsequent reoperation. Adequate surgical margin was defined as any negative margin greater than 2 mm. RESULTS: The group with complete resection of 4 to 6 additional margins had a subsequent reoperation rate of 17.7%, whereas the group with selective resection of 1 to 3 additional margins and the standard lumpectomy group had a subsequent reoperation rate of 32.5% and 38.7%, respectively, because of inadequate margins. The mean total excised specimen volume in the 3 groups was 129.19, 46.04, and 37.44 cm3, respectively. CONCLUSIONS: The complete resection of 4 to 6 additional margins during the initial BCT resulted in the lowest subsequent reoperation rate, and the largest total volume specimen excised among the 3 techniques studied.     

Factors associated with local breast cancer recurrence after lumpectomy alone

Background: The purpose was to determine the rate of local breast relapse in patients with breast cancer uniformly treated with partial mastectomy but without postoperative radiotherapy and without systemic adjuvant therapy. We also systematically examined the factors associated with local recurrence to determine whether a low-risk subgroup existed. Methods: A retrospective review of a prospectively followed (median, 8 years) cohort of 293 patients was performed. The end-point was ipsilateral local breast cancer recurrence. The patient's age, tumor size, nodal status, estrogen and progesterone receptor status, histology, and tumor and nuclear grade were studied, as were the presence and amount of carcinoma in situ and the presence of tumor emboli using univariate Kaplan-Meier and Cox step-wise multivariate analyses. Results: The overall local relapse rate was 26% (77 recurrences). Univariate factors significantly associated with decreased local relapse included older age, negative nodes, small tumor size, positive estrogen receptor status, and absence of tumor emboli. Significant multivariate variables were age, nodal status, estrogen receptor status, absence of comedo carcinoma in situ, and tumor emboli. A low-risk subgroup of 66 patients was defined with a 6% 10-year local recurrence rate. Conclusion: Important patient and tumor variables associated with local breast cancer relapse after breast-conserving surgery can define a low-risk subgroup.     

The Consequence of Multiple Re-Excisions to Obtain Clear Lumpectomy Margins in Breast Cancer Patients

Background Microscopically clear lumpectomy margins are critical for optimizing local control with breast conservation for cancer. Re-excisions are often necessary to achieve clear surgical margins. Factors that contribute to nonnegative margins and necessitate re-excision may increase the risk of local recurrence. Methods Patients who were treated with breast conservation for breast cancers were identified from a prospective database maintained by one of the authors. Factors associated with local recurrence were evaluated in 459 consecutive patients with attention to the number of re-excisions required to obtain clear margins. Results Twenty-eight patients (5%) developed local recurrences at a mean follow-up of 78 months. In multivariate analysis, local recurrence was most significantly associated with the omission of radiotherapy (19% vs. 5%; relative risk [RR], 3.64; 95% confidence interval, 1.6–8.2), followed by young age (52 vs. 58; 95% confidence interval, −.83 to −10.6 years) and the number of re-excisions required to obtain clear margins (none, 4%; one, 7% [RR, 2.05; 95% confidence interval, .86–4.89]; two or more, 17% [RR, 5.20; 95% confidence interval, 1.44–18.8]). Tumor size, the number of involved nodes, pathology, and adjuvant chemotherapy were not significantly related to local recurrence. Conclusions The risk of local recurrence after breast conservation for breast cancer increases progressively with the number of re-excisions needed to achieve clear margins. Patients in whom the cancer is fully excised with clear margins in the first excision will have less of a chance of local recurrence compared with patients who need further re-excision to achieve clear margins.     

Interest in cavity shaving in breast conservative treatment does not depend on lumpectomy technique

In breast conserving surgery (BCS), the usefulness to perform systematic cavity shaving is actively debated. Some investigators argued that systematic cavity shaving could avoid surgical re-excision and make diagnosis of unexpected multifocality. Others argued that usefulness of cavity shaving depends on volumes of resection.In this study one hundred patients undergoing BCS with systematic cavity shaving were included. Margins less than 3 mm were considered to be insufficient. We tested clinico-pathological characteristics in order to identify predictive model of cavity margin shaving utility and we sought to determine if cavity margin shaving usefulness depends on volumes of resection. We showed that cavity shaving avoids the need for re-excision in 24% of cases as well as diagnosis of multifocality in 6% of cases. However, the clinical usefulness of cavity shaving was not related to the volumes of resection.     

Factors associated with local breast cancer recurrence after lumpectomy alone: Postmenopausal patients

Background: We have been following a cohort of patients who underwent a lumpectomy without receiving adjuvant radiotherapy or adjuvant systemic therapy. We now report the experience of a postmenopausal subgroup. Methods: The postmenopausal subgroup included 244 patients accrued between 1977 and 1986 and followed up. The end point was ipsilateral local breast cancer recurrence. The factors studied were the patient’s age in years; tumor size (in mm); nodal status (N-, Nx, N+); estrogen and progesterone receptor status (<10, ≥10 fmol/mg protein); presence or absence of lymphovascular/perineural invasion; presence or absence, and type, of DCIS (none, non-comedo, comedo); percentage of DCIS; histological grade (1,2,3); and nuclear grade (1,2,3). Univariate analyses consisted of Kaplan-Meier plots and the Wilcoxon (Peto-Prentice) test statistic; the multivariate analyses were step-wise Cox and log-normal regressions. Results: The median follow-up of those patients still alive was 9.1 years, and the overall relapse rate was 24% (59/244). The univariate results indicated that the characteristics of smaller tumor size, negative nodes, positive ER status, and no lymphovascular or perineural invasion were associated with significantly (P<.05) lower relapse. From the multivariate analyses, the factors lymphovascular or perineural invasion, age, and amount of DCIS were all significantly associated with local relapse with both Cox and log-normal regressions. Additionally, there was weak evidence of an association between ER (P=.08 in the Cox regression and in the log-normal) and nodal status (P=.09 in the log-normal regression) with local relapse. We also are able to define a low-risk subgroup (N-, age ≥65, no comedo, ER positive, no emboli) with a crude 10-year local recurrence rate of 9%. Conclusion: With longer follow-up, and for postmenopausal patients, there continues to be support for the theory that local relapse is affected by the factors lymphovascular or perineural invasion, age, amount of DCIS, ER, and nodal status. A low risk subgroup has been identified. Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, March 16–19, 2000, New Orleans.     

Local recurrence in lumpectomy patients after imprint cytology margin evaluation

BACKGROUND: This is a follow-up study to our previously reported data on local recurrence rates in patients whose lumpectomy margins were evaluated by intraoperative imprint cytology (IIC(M)). The purpose of this study was to compare local recurrence rates for patients whose lumpectomy margins were evaluated with IIC(M) with local recurrence rates of those not evaluated by IIC(M). METHODS: A total of 1713 patients underwent lumpectomy treatment for breast cancer from 1988 to 2001 were prospectively entered into a computerized database and subsequently included in this study. Of the patients, 520 (group 1) had their surgery performed at an outside institution where conventional margin analysis was performed. Another 1193 (group 2) had their surgery performed at our institution where margins were evaluated by IIC(M). For each histologic type and for the overall sample, probabilities of recurrence with time were estimated using the method of Kaplan and Meier. RESULTS: IIC(M) overcomes sampling error inherent in the frozen section analysis and results in a diminished incidence of overall 5-year local recurrence from 8.8% to 2.8% (P <0.0001). The recurrence rates for each respective histologic subtype are reported for both absolute recurrences and probability of recurrence with time. CONCLUSIONS: IIC(M) provides an accurate evaluation of lumpectomy margins for patients undergoing breast-conservation treatment. IIC(M) was associated with an overall lower local recurrence rate. This series defined the utility of intraoperative imprint cytology for evaluation of margins in patients undergoing breast-conservation treatment.     

The pancake phenomenon contributes to the inaccuracy of margin assessment in patients with breast cancer

BACKGROUND: To determine the effect on margin evaluation for patients with breast cancer, we prospectively quantified the "flattening" of the breast specimen after surgical removal. METHODS: The volume and height of 100 consecutive breast biopsy specimens were recorded independently by the operating surgeon and the pathologist. Five factors were analyzed that were thought to contribute to changes in specimen dimensions: patient age, breast tissue density, mammographic lesion type, specimen size, and the use of compression during specimen radiography. RESULTS: After surgical removal, mean volume and height of the breast specimens decreased from 46 cm(3) to 29 cm(3) (30%) and from 2.6 cm to 1.4 cm (46%), respectively. Flattening of the breast specimens occurred in all subgroups studied. CONCLUSIONS: Breast specimens are flattened after surgical removal, losing almost 50% of their original height. This "pancake" phenomenon has important implications for the accuracy of margin analysis.     

Use of touch preps for diagnosis and evaluation of surgical margins in breast cancer

Background: The best cosmetic results with conservative breast surgery are obtained at the time of initial excisional biopsy. The usefulness of the touch prep (TP) technique was evaluated for accuracy in diagnosis as well as in evaluation of margins at the time of original breast biopsy. Methods: Four hundred twenty-eight consecutive patients with breast masses seen from January 1993 to December 1994 were evaluated prospectively using TP. Results: Three hundred forty-five benign and 83 malignant tumors were evaluated. Tumors ranged in size from microscopic to 8 cm. Pathologic diagnosis was correct as compared to permanent section in 99.3%. The three carcinomas missed on TP were focal and in situ. Sensitivity was 96.39%, and specificity was 100%. Positive predictive value was 100%, and negative predictive value was 99.3%. For margin evaluation, the sensitivity and specificity were both estimated to be 100%. Conclusions: TP has the advantage of being a simple, quick (2 to 3 minutes), safe (no loss of diagnostic material), and accurate method for diagnosis and estimation of tumor margins at the time of the original surgery.Presented at the 49th Annual Cancer Symposium of The Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

Effect of reexcision on the success of breast-conserving surgery

Background: The success of lumpectomy and radiotherapy is dependent on minimizing the residual tumor burden in the breast. Histologic margin status is one measure of the extent of residual tumor. This study was undertaken to determine the success rate of a single conservative lumpectomy in obtaining negative margins and to evaluate the incidence of residual tumor after biopsies with positive or unknown margins. Methods: This is a retrospective study covering a 5-year period (June 1988–June 1993). Results: Three hundred sixteen women had lumpectomies. In 239, lumpectomy was the initial operation after a positive fine-needle aspiration or as a diagnostic procedure. Thirteen cases had positive margins. Reexcision was performed in 90 cases. The indication for reexcision was a positive margin in 42 cases (4 with gross tumor) and unknown margin status in 48. Nineteen of the reexcisions for positive margins and 20 of the reexcisions for unknown margins contained residual tumor. Eighty-six (96%) of the 90 reexcised patients underwent breast preserving surgery. Patient age, menopausal status, histologic tumor type, tumor size, and clinical presentation were not predictive of residual tumor. Conclusions: The need for reexcision does not preclude breast preservation. Because single-stage lumpectomy is successful in achieving negative margins in 95% of patients, diagnostic biopsy without margin evaluation should be abandoned to avoid routine reexcision.Results of this study were presented at the 47th Annual Meeting of The Society of Surgical Oncology, March 17–20, 1994, Houston, Texas, USA.     

Cytologic evaluation of lumpectomy margins in patients with ductal carcinoma in situ: Clinical outcome

Backround: Breast conservation therapy is controversial for ductal carcinoma in situ (DCIS) due to recently reported high recurrence rates. We believe that cytologic evaluation of lumpectomy margins improves efficiency and leads to a lower recurrence rate following lumpectomy for DCIS. Methods: A prospectively accrued database of 1255 breast cancer patients at the H. Lee Moffitt Cancer Center and Research Institute was found to have 218 patients with DCIS (17.4%). Of those 218 cases, 114 were treated with lumpectomy, axillary dissection, and radiation therapy; the remaining 104 patients were treated with mastectomy with or without reconstruction. Imprint cytology was used to evaluate all lumpectomy margins. Permanent sections and imprint cytology were reviewed by the same pathologist. Results: All lumpectomy specimens (116 tumors in 114 patients) were evaluated. The median follow up was 57.5 months (range 2–110 months). One hundred and three patients with 104 tumors were selected on the basis of pure DCIS (with or without microinvasion), and treated with lumpectomy, axillary dissection and radiation therapy. Of the 104 tumors utilizing attempted breast conservation therapy, 7 (6.6%) required mastectomy. There were 6 recurrences (6.1%) with a median time for recurrence of 47.5 months (range 27–85 months); four recurrences were comedo and two were noncomedo at original diagnosis. Conclusions: The determination of lumpectomy margins in DCIS patients using imprint cytology leads to an overall recurrence rate of 6.1% with reduction in operative time, and re-excision rate. Significant recurrence rates were associated with microinvasion and multifocal tumors (28%) versus simple DCIS at 5 years. Breast conservation therapy and surgical margin determination with imprint cytology for DCIS is a cost-effective and reliable method of treatment for simple DCIS.     

Influence of breast cancer margin assessment method on the rates of positive margins and residual carcinoma

BACKGROUND: We hypothesized that the method of breast cancer margin assessment may be associated with different rates of positive margins and residual carcinoma. METHODS: A total of 178 breast cancer specimens were divided into 2 groups (A and B) based on the margin assessment method used. Rates of positive margins, re-excision, and residual carcinoma at re-excision were compared and analyzed statistically. RESULTS: At least 1 margin was positive in 64.7% in group A and in 65.2% in group B. At directed re-excision 54% in group A and 51% in group B had residual carcinoma. The lateral margin was positive in 44% in group A compared with 26% in group B (P = .06). The posterior margin was positive in 19% in group A and in 51% in group B (P = .001). CONCLUSIONS: Two different breast cancer specimen margin assessment methods had comparable rates of positive margins and residual carcinoma at re-excision. Different patterns of specific margin positivity suggest that the method of margin assessment may alter results.     

Atypical Ductal Hyperplasia at Margin of Breast Biopsy—Is Re-Excision Indicated?

Background Atypical duct hyperplasia (ADH) observed during core needle biopsy is associated with a high rate of cancer upon excision. Controversy exists regarding the need to re-excise ADH involving a margin. The purpose of this study was to determine the rate of residual pathology in patients that underwent re-excision for ADH involving the margin. Methods In a retrospective review of the pathology database from 1 January 2000 to 1 June 2006, we identified 44 lumpectomy specimens with ADH involving the margin; 24 patients (55%) had a re-excision. Slides were reviewed to verify the diagnosis of ADH near the margin and the presence of residual disease on re-excision associated with the biopsy cavity. Results Patients had pure ADH (15, 63%), ADH and ductal carcinoma in situ (DCIS) (7, 29%) or ADH with invasive carcinoma (2, 8%). Residual ADH or cancer was found in 14 of 24 patients (58%). Of 15 patients with pure ADH, 6 (40%) had residual pathology: ADH (2), DCIS (2) and invasive carcinoma (2). In this group, 27% of patients were reassessed as having DCIS or invasive carcinoma. Of the 9 patients with cancer, 8 (89%) had residual disease in the form of ADH (4) or DCIS (4). Conclusions ADH found at the margin of a lumpectomy specimen is associated with a high rate of residual ADH and cancer. Over one quarter of the patients with an initial diagnosis of ADH were reassessed as having DCIS or invasive carcinoma. Re-excision in all patients with ADH involving the margin is recommended.     

影响乳腺癌患者保乳手术边缘阳性因素的临床研究

目的探讨乳腺癌的临床病理学特征对保乳手术边缘阳性的影响。方法189例预行保乳手术术(BCT)的原发性乳腺癌患者,分析她们的临床特征(年龄,活检类型)和病理学特征(肿瘤大小,组织学类型,激素受体状态,HER2状态,和腋窝淋巴结状态)与阳性手术边缘的关系。结果189例患者中本组室心针肿脾物案例活检确诊79例,门诊或手术中切除活检确诊128例。61例手术边缘阳性(32.3%)。结论本研究的结果揭示:肿瘤直径大于2cm,腋窝淋巴结阳性PR阳性和年龄小于50岁是乳癌保乳手术边缘阳性的高危因素对1999年1月～2004年7月189例乳腺癌患者按受保乳手术进行回顾性分析,并总结手术切口边保阳性与临床特征病理案组但表现及激素受体状态的关系。     

Factors which affect the use of lumpectomy and mastectomy in an underinsured,safety net hospital population

Background

This study was performed to evaluate variables that affect the use of mastectomy and lumpectomy in an underinsured population.

Methods

A retrospective review of all patients who underwent breast cancer operations from July 2001 to February 2011 at a safety net hospital was performed. Univariate and multivariate analyses were performed to identify variables, which were associated with the type of operation.

Results

Of the 412 patients, 81% of the patients were underinsured or uninsured. Most patients (58%) presented with clinical stage 2A/B disease. Mastectomy was performed in 37% of patients and lumpectomy in 63%. In multivariate analysis, clinical tumor size (P = .035) and pathologic stage (P = .003) remained associated with mastectomy, while use of preoperative chemotherapy (P = .004) and type of surgeon (P = .001) was associated with lumpectomy.

Conclusions

Most patients underwent lumpectomy despite later stage at presentation. Preoperative chemotherapy was associated with increased likelihood of lumpectomy.     

eRFA: Excision Followed by RFA—a New Technique to Improve Local Control in Breast Cancer

Introduction Excision followed by RFA (eRFA) may allow improved cosmesis while ensuring negative margins in patients with breast cancer. This technique utilizes heat to create an additional tumor-free zone around the lumpectomy cavity. We hypothesized that eRFA will decrease the need for re-excision of inadequate margins.Methods Between July 2002 and January 2005, we conducted a multiphase trial of RFA of prophylactic mastectomy specimens and of women desiring lumpectomy. In both models, a lumpectomy was performed, the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100°C for 15 min. Whole mount slides were used to measure the zone of ablation for ex vivo specimens. Hematoxylin and eosin staining of in vivo lumpectomy margins <3 mm was considered inadequate.Results Nineteen prophylactic mastectomy ablations revealed a consistent perimeter of ablation. Forty-one patients (mean age 63 ± 14 years) had an average tumor size of 1.6 ± 1.5 cm underwent in vivo eRFA, and 25% had inadequate margins: one focally positive, one <2 mm, eight <1 mm and one grossly positive. Only the grossly positive margin was re-excised. Overall complication rate of in vivo ablations was 7.5%. Twenty-four of 41 patients did not have post-eRFA XRT. No in-site local recurrences have occurred during a median follow-up of 24 months (12–45 months). Two patients have occurred elsewhere.Conclusions The ex vivo ablation model reliably created a 5–10 mm perimeter of ablation. In vivo, this zone reduced the need for re-excision for inadequate margins by 91% (10/11). Short-term follow-up suggests that eRFA could reduce re-excision surgery and local recurrence.     

Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy

BACKGROUND: Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. METHODS: In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). RESULTS: No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates (P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. CONCLUSIONS: BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.