Predictors of Surgical Margin Status in Breast-Conserving Surgery Within a Breast Screening Program

Background  Breast-conserving surgery (BCS) requires clear surgical margins to minimize local recurrence. We sought to identify groups of patients at higher risk of involved margins who might benefit from preoperative counselling and/or more generous excision at the first operation. Methods  We reviewed demographic, clinical, radiological and pathological records of all women diagnosed with ductal carcinoma in situ (DCIS) or invasive cancer (IC) through a population-based breast screening program in Melbourne, Australia between 1994 and 2005. Results  A total of 2,160 women were diagnosed with DCIS or IC. We excluded 199 who had mastectomy (TM) as initial procedure or had missing data. Three hundred and thirteen had a diagnostic biopsy. Of 1,648 women who had BCS after a preoperative diagnosis of DCIS or IC, 13.5% had involved margins, 16.6% had close (≤1 mm), and 69.8% clear (>1 mm) margins. Of the patients, 281/1,648 (17.1%) underwent re-excision, of whom 93 (33.1%) had residual disease identified. Mammographic microcalcifications (P < 0.0001), absence of a mammographic mass (P = 0.002), presence of DCIS (P < 0.0001), high tumour grade (P < 0.0001), large size (P < 0.0001), multifocal disease (P < 0.0001) and lobular histology (P = 0.005) were associated with involved margins. Microcalcifications (odds ratio [OR] 1.97), large size (OR 4.22) and multifocal disease (OR 2.85) were independently associated with involved margins. Residual disease was associated with involved margins (P < 0.0001), presence of DCIS (P = 0.05) and large tumour size (P = 0.01). Conclusion  After BCS, patients with mammographic microcalcifications, larger tumour size and multifocal tumours are more likely to have involved margins. Patients with involved margins, large tumour size and/or a DCIS component are more likely to have residual disease on re-excision.     

Ductal Carcinoma-In-Situ: Long-Term Results of Breast-Conserving Therapy

Background: The role of breast-conserving therapy (BCT) in the management of ductal carcinoma-in-situ (DCIS) is controversial because of reported high recurrence rates. We reviewed our experience to determine whether the rate and pattern of locoregional recurrence after BCT were similar in patients with DCIS and patients with early-stage (T1) invasive breast tumors and whether local recurrence affected survival.Methods: Between 1973 and 1994, 87 patients with DCIS alone, 22 patients with DCIS with microinvasion (DCIS-M), and 646 patients with invasive breast cancer 2 cm or smaller in diameter were treated with BCT (wide local excision with radiotherapy) at The University of Texas M. D. Anderson Cancer Center. Survival was calculated by the Kaplan-Meier method. The median follow-up times were 11 years for patients with DCIS alone, 12 years for patients with DCIS-M, and 8 years for patients with invasive breast cancer.Results: Eleven (13%) of 87 patients with DCIS and 5 (23%) of 22 patients with DCIS-M had developed locoregional recurrences at follow-up. Two patients with DCIS with locoregional recurrence died of breast cancer. Of the 646 patients with invasive breast cancer, 56 (9%) had a locoregional recurrence, and 16 (2%) died of breast cancer. The median time to locoregional recurrence was significantly longer in patients with DCIS or DCIS-M (9–10 years) than patients with invasive tumors (5 years).Conclusions: DCIS is a favorable disease with an excellent long-term survival. The locoregional recurrence rate in patients with DCIS treated with BCT is similar to that in patients with early-stage invasive breast cancer treated with BCT, but time to locoregional recurrence is significantly longer in patients with DCIS. In patients with DCIS treated with BCT, intense surveillance for locoregional recurrence needs to be maintained for the patients lifetime.Presented at the 53rd Annual Meeting of the Society of Surgical Oncology, New Orleans, Louisiana, March 16–19, 2000.     

Telomerase Activity Levels for Evaluating the Surgical Margin in Breast-Conserving Surgery

To evaluate the efficiency of measuring telomerase activity levels in clinical diagnosis, we performed a semiquantitative analysis of telomerase activity in breast tumors and compared the results with the histological findings. Breast tissue adjacent to areas of cancer were also serially resected and checked for telomerase activity. The amount of telomerase activity in the breast cancers ranged widely, from 0.36 to 1 180 units/μg, with 31 of the 34 (91.2%) showing a value above 1.0 unit/μg. None of the normal breast tissues including mastopathy, and only 4 (23.5%) of 17 benign breast masses had values above 1.0 unit/μg. Telomerase activity was detectable in serial sections of adjacent tissues as far as 10 mm from the macroscopic tumor margin with histologically detectable cancer cells. Furthermore, telomerase activity was detectable in the scrape specimens obtained from the stump of the surgical margins for breast-conserving surgery, and this activity was in accordance with the histological findings. These findings show that conducting a semiquantitative assay of telomerase activity is useful for evaluating the surgical margin in breast-conserving surgery. Received: May 10, 2000 / Accepted: September 26, 2000     

Patient age and positive margins are predictive factors of residual tumor on mastectomy specimen after conservative treatment for breast cancer

AimsTo determine factors predictive of the presence of residual tumor on the specimen from mastectomy performed after conservative treatment for breast cancer in order to limit potentially unnecessary mastectomies (free of residual lesions).Materials and methods294 patients treated in 2 expert centers for breast cancer with breast-conserving therapy (BCT) followed by mastectomy, according to French recommendations, were investigated between January 1, 1998 and January 1, 2005. Patients with residual tumor on the mastectomy specimen were compared with patients whose mastectomy specimens did not reveal any residual tumor. All the clinical risk factors (age, previous history of breast cancer, tumor focality) and histological risk factors (tumor size, histological type, positive margins, estrogen and progesterone receptor expression, histological grade) for residual tumor after BCT were compared between the 2 patient groups.ResultsOf the 294 patients studied, 202 (68.71%) mastectomies had residual tumor and 92 (31.29%) were tumor-free. Four predictive factors for residual tumor were found in the univariate analysis: age under 45 years (p = 0.01), absence of estrogen receptor expression (p = 0.05), positive margins (p = 0.01), and presence of lymph node metastases (p = 0.05). The multivariate analysis revealed only 2 independent risk factors that were significantly associated with increased risk of residual tumor on the mastectomy specimen: age under 45 years (p = 0.05) and presence of positive margins on the lumpectomy specimen (p = 0.05).ConclusionYoung age of patients (under 45-years-old) and presence of positive margins on the operative specimen are independent risk factors of residual tumor after conservative treatment of breast cancer.     

Presence of Lobular Carcinoma In Situ Does Not Increase Local Recurrence in Patients Treated with Breast-Conserving Therapy

Background  Lobular carcinoma in situ (LCIS) is known to be a risk factor for the development of invasive breast cancer. Debate continues as to whether LCIS is also a precursor lesion. We hypothesized that, if LCIS were a precursor, its presence in the lumpectomy specimen, particularly at the margin, could increase local recurrence (LR) after breast-conserving therapy (BCT). Methods  2894 patients treated with BCT for ductal carcinoma in situ (DCIS), stage I or II breast cancer between 1/80 and 5/07 were identified. Patients with DCIS or invasive cancer at the margins or those receiving neoadjuvant therapy were excluded. Group A had 290 patients with LCIS in the lumpectomy; 84 had LCIS at the final margin. Group B included 2604 patients with no evidence of LCIS. Results  Median patient age in group A and B was 57 and 58 years, respectively (P = 0.05); 12% and 13%, respectively, of patients in group A and B had margins <2 mm (P = NS). The histologic distribution of tumor types in group A was lobular in 47.2%, ductal in 34.5%, DCIS in 11.4%, and other invasive histologies in 6.9%, compared with 4.1%, 76.3%,13.6%, and 6.0% for group B, respectively (P < 0.0001). There was no significant difference between the groups in tumor–node–metastasis (TNM) stage. The crude rate of LR was 4.5% in group A and 3.8% in group B (P = NS). Five- and 10-year actuarial LR rates for LCIS at the margin were 6% and 6%, 1% and 15% for LCIS present but not at the margin, and 2% and 6% for no LCIS (P = NS), for group A and B, respectively. In multivariate analysis, menopausal status and adjuvant therapy use were significant predictors of LR. LCIS, either in the specimen or at the margin, was not significantly associated with LR. Conclusion  Presence of LCIS, even at the margin, in BCT specimens does not have an impact on LR. Re-excision is not indicated if LCIS is present or close to margin surfaces. These findings do not support consideration of LCIS as a precursor to the development of invasive lesions. Abstract presentation at the Scientific Session of the 61st Annual Cancer Symposiumof the Society of Surgical Oncology, Chicago, IL, March 13–16, 2008.     

Frozen Section Analysis for Intraoperative Margin Assessment During Breast-Conserving Surgery Results in Low Rates of Re-excision and Local Recurrence

Background Negative surgical margins minimize the risk of local recurrence after breast-conserving surgery. Intraoperative frozen section analysis (FSA) is one method for margin evaluation. We retrospectively analyzed records of patients who received breast-conserving therapy with intraoperative FSA of the lumpectomy cavity to assess re-excision rates and local control. Methods Records were retrospectively reviewed for individuals who underwent breast-conserving surgery for ductal carcinoma in situ (DCIS) or invasive carcinoma between 1993 and 2003. Inclusion criteria were a minimum of 2 years follow-up and intact tumor at the time of operation. The major outcome measure was local recurrence. The Kaplan-Meier test was used to evaluate local recurrence rates between groups. Results 290 subjects with an average age of 57.2 years (range 27–89) underwent 292 lumpectomies with FSA. 11.3% had DCIS, 73.3% had infiltrating ductal, 5.8% had infiltrating lobular, and 9.6% exhibited other forms of invasive carcinoma. 70 subjects underwent additional resection at the time of breast surgery, 16 underwent subsequent re-excision, and 17 underwent subsequent mastectomy. At a median follow-up of 53.4 months (range 5.8–137.8), there were six local recurrences (2.74%) in patients who had breast-conserving procedures and two local recurrences in patients who underwent mastectomy. There were no statistically significant associations among local recurrence rate, tumor size, nodal status, or overall stage. Local recurrences were higher in patients with DCIS compared with invasive carcinoma, and tumors >2cm. Conclusions Intraoperative FSA allows resection of suspicious or positive margins at the time of lumpectomy and results in low rates of local recurrence and re-excision. The low local recurrence rate reported here is comparable to those reported with other margin assessment techniques.     

Factors Affecting Successful Breast Conservation for Ductal Carcinoma in Situ

Background Successful breast-conserving therapy in DCIS is restricted by high rates of residual disease resulting in the need for radiotherapy and/or re-excision. This study identifies patients with DCIS who are most at risk of compromised margins and of residual disease. Methods All patients undergoing breast-conserving surgery for DCIS over a 6-year period were included. Method of diagnosis, mammographic size, pathological size, DCIS-margin distance and residual disease on re-excision were analysed. Results One hundred and thirty-five patients underwent initial breast-conserving surgery for DCIS. The compromised margin rate was 72%, and the rate of residual disease on re-operation was 54%. On univariate analysis, underestimation of pathological size by mammography by >1 cm occurred in 40% of those with compromised margins undergoing a therapeutic operation compared to only 14% of those with clear margins (P = 0.02). However, on multivariate analysis only pathological size (P < 0.0001, OR = 1.0,95% CI 1.037–1.128) and lack of a preoperative diagnosis by core biopsy (P < 0.0001, OR = 5.3,95% CI 1.859–15.08) were predictive of compromised margins. The presence of residual disease on re-excision was associated with increasing pathological size (P < 0.0001, OR = 1.085,95% CI 1.038–1.134) and decreasing DCIS-margin distance (P = 0.03, OR = 6.694,95% CI 1.84–37.855). Twenty-nine percent (n = 13/45) of lesions ≤3 cm compared to 84% (n = 27/32) of lesions >3 cm had residual disease on re-operation (P < 0.0001). Residual disease was present in 62% (n = 34/55), 64% (n = 7/11) and 17% (n = 2/12) of patients with DCIS-margin distances ≤1, 1–2 and 2–5 mm, respectively. Conclusion Considerable underestimation of DCIS extent by mammography occurs in a high proportion of patients with compromised margins in breast conservation. Patients at particularly high risk of residual disease on re-excision are those with lesions >3 cm and those with DCIS-margin distances of ≤ 2mm.     

Application of Ultimate Oncoplastic Surgery in Breast-Conserving Surgery

ObjectiveTo investigate the application of oncoplastic surgery in breast-conserving surgery.MethodsWe retrospectively analyzed the clinical data of 103 breast cancer patients who underwent breast-conserving surgery in the First Affiliated Hospital of Henan University. All the patients were female whose tumor volume-to-breast volume ratio was greater than 20%. Fifty-two patients were treated with oncoplastic breast-conversing surgery (observation group), and 51 patients were treated with traditional breast-conserving surgery (control group). The volume of resected tissue, subjective satisfaction with breast shape, objective score of breast shape, and follow-up were compared between the two groups.ResultsIn the observation group, the weight of resected breast tissue was 64.2–172.1 g, with a median of 98.7 g. In the control group, the weight of resected breast tissue was 67.5–175.7 g, with a median of 102.3 g. After 12 months of follow-up, the subjective satisfaction rate and objective score of breast shape in the observation group were significantly better than those in the traditional breast-conserving surgery group (P < 0.05). There was no recurrence, metastasis, or death in the two groups. There was no significant difference in postoperative complications between the two groups (P > 0.05).ConclusionOncoplastic breast-conserving surgery leads to better cosmetic results and a more satisfactory clinical results.     

Role for Intraoperative Margin Assessment in Patients Undergoing Breast-Conserving Surgery

Background Positive/close margins are associated with higher in-breast failure rates after breast-conserving surgery (BCS). We investigated whether intraoperative margin assessment aids in obtaining negative margins, and to evaluate the local control thus achieved. Methods Between 1994 and 1996, 264 patients underwent BCS for stages 0–III breast cancer [invasive, n = 200; ductal carcinoma in situ (DCIS), n = 64]. Intraoperative margin assessment included gross tissue inspection, specimen radiography, with or without frozen section. Results Ninety-two patients (46%) with invasive cancer and 24 (38%) with DCIS had positive/close margins on the permanent section analysis of their initial surgical specimens. Fifty-eight patients (29%) with invasive cancer and six (9%) with DCIS had initial positive/close margins, and were rendered margin-negative by intraoperative analysis and immediate re-excision. Final margins on permanent pathology were positive/close in 52 patients (20%): 34 patients (17%) with invasive cancer and 18 patients (28%) with DCIS. By multivariate analysis, excisional biopsy for diagnosis, larger tumor size, and multifocality were associated with final positive/close margins. Of these 52 patients, 23 underwent a second operation to achieve widely negative margins (13 completion mastectomies, 10 re-excisions). The 5-year ipsilateral breast recurrence-free survival rates after BCS and radiation were 99% for invasive cancer (n = 167) and 100% for DCIS (n = 27). Conclusions Intraoperative assessment of margins assisted in identifying positive/close margins and allowed over a quarter of the patients to be rendered margin-negative with intraoperative re-excision at their original operation. This approach resulted in excellent local control in patients treated with BCS and radiation.     

Pilot Trial of Cryoprobe-Assisted Breast-Conserving Surgery for Small Ultrasound-Visible Cancers

Background: Stereotactic and ultrasonography-guided large core needle biopsy has replaced wire localization biopsy as the diagnostic method of choice. Lumpectomy alternatives are being sought to eliminate the need for preoperative wire localization, to facilitate easier and more accurate resection, and to decrease positive margin rates. Cryoprobe-assisted lumpectomy (CAL) was investigated as an alternative.Methods: Patients with ultrasonographically visible breast cancers that otherwise would have required wire localization participated. Before lumpectomy, a cryoprobe (Visica; Sanarus, Pleasanton, CA) was inserted through a 3-mm skin incision and directed by ultrasonography through the center of the tumor. An ice ball was created that enveloped the tumor plus an adjacent 5–10 mm of sonographically normal breast tissue.Results: Twenty-four CAL procedures were performed and all lesions were successfully localized. Mean (±SD) tumor size was 1.2 ± .4 cm (range, .7–2.0 cm). Mean dimensions of the ice ball before excision were 3.9 ± .3 cm by 2.5 ± .5 cm, and the ice margin around the tumor was 8 ± 2 mm. The size of the ice ball was controlled to the millimeter, and the ice ball itself provided a precise template around which to dissect. The margin re-excision rate was 5.6% among patients with an ice margin greater than 6 mm.Conclusions: CAL is a superior alternative to wire localization. Ultrasonographic visualization of the ice ball allows the size of the margin and tissue resected to be individually tailored and accurate within millimeters. The created template allows a precise lumpectomy, adding a dimension of control not previously realized with any other technology.     

乳腺癌保乳手术中乳房缺损的修复方法

目的综述乳腺癌保乳手术中乳房缺损的修复方法。方法分析近年来相关文献,对有关乳腺癌保乳手术中乳房缺损的修复方法、适应证、切口选择以及优缺点进行分析。结果保乳手术后部分患者存在乳房畸形,美容效果不佳。如何选择手术切口、怎样修复肿瘤切除后的乳房缺损,以获得较好的美容效果是外科手术中的焦点问题。将乳房整形技术应用于保乳手术,可明显改善美容效果。结论选择合适的早期乳腺癌患者采用乳房整形技术进行保乳手术治疗,安全、有效,术后患者对乳房外形及整体美容效果满意度高,是值得推荐的一种技术。     

Margins! Margins. Margins? How Important Is Margin Status in Breast-Preserving Therapy?

Margin status is surely a prognostic factor in patients undergoing breast-conserving therapy, but its impact is probably overestimated in case of adequate adjuvant radiotherapy. Radiotherapy improves local control after excision of the primary tumor in all subgroups of patients. There is, in contrast, no evidence that a certain margin width or a re-resection improves local control.     

Association of Clinical and Pathologic Variables with Lumpectomy Surgical Margin Status after Preoperative Diagnosis or Excisional Biopsy of Invasive Breast Cancer

Purpose To evaluate the impact of preoperative diagnosis in obtaining negative lumpectomy margins. Materials and Methods Five hundred and thirty five patients who underwent breast conserving therapy for stage I/II cancer from 1971 to 1996 were included in this IRB-approved retrospective analysis. Three hundred and ninety five patients had a defined inked margin status after initial excision. The following factors were evaluated for correlation with margins at initial excision: age (< or >45), grade (3/1 or 2), family history (present/absent), histology (lobular/other), estrogen receptor (ER) status, presence of extensive intraductal carcinoma (EIC), presence of lymphovascular invasion (LVI), and biopsy type (excisional/preoperative). Results Biopsy type (P < 0.0001), EIC (P = 0.002), ER status (P = 0.02), lobular histology (P = 0.02) and age (P = 0.02) were significantly correlated with initial margin status among the entire group. For patients who underwent preoperative diagnostic biopsy, 52% (35/67) had negative initial margins as compared to 29% (94/328) for excisional biopsy. Among patients who underwent preoperative biopsy, only lobular histology (P = 0.04) and LVI (P = 0.04) were related to initial margin status. The rate of re-excision was 34% for patients diagnosed preoperatively versus 61% with excisional biopsy (P < 0.0001). The percentage of patients with negative final margin status was similar with either core/needle or excisional biopsy (79 and 78%, respectively). Conclusions Preoperative diagnosis is the most significant predictor of initial margin status in patients undergoing breast conservation. Patients with lobular histology may require improved preoperative and/or intraoperative assessment to increase the rate of negative margins at initial excision.     

Identifying patients at risk of compromised margins following breast conservation for lobular carcinoma

BACKGROUND: The association of invasive lobular carcinoma with high rates of compromised margins in breast conservation makes choice of operation for these patients difficult. We sought to identify patients at risk of compromised margins following breast conservation surgery. METHODS: We reviewed all patients with invasive lobular and invasive ductal carcinoma over a 5-year period (1999-2004). The imaging, pathology and surgical details of patients with invasive lobular carcinoma undergoing breast conservation were analyzed. RESULTS: A total of 991 patients with invasive ductal carcinoma and 150 patients with invasive lobular carcinoma were identified. Lobular carcinomas had a compromised margin rate of 49% (n = 38/77) in breast conservation compared to 24% (n = 143/588) of ductal carcinomas (P < .0001). Mammographic size (P = .017), pathological size (P = .01), age (P = .03), multifocality (P < .0001), and lymphovascular invasion (P = .015) were significantly associated with compromised margins. CONCLUSION: Invasive lobular carcinoma has a 49% rate of compromised margins following breast conservation. Mammographic size greater than 1.5 cm and young age were preoperative factors predictive of compromised margins.     

Tubular Carcinoma of the Breast: A Histologic Subtype Indicative of Breast-Conserving Therapy

We reviewed the clinical and pathologic features of pure tubular carcinoma of the breast with particular emphasis on the reported risk factors associated with local recurrences and survival following breast-conserving therapy. Of 1653 cases of invasive breast cancer, 12 (0.7%) were identified as pure tubular carcinoma. Clinical/pathologic features of pure tubular carcinoma were compared with those of T1 invasive carcinoma of all other histologic types (T1 IC). Of the 12 patients with pure tubular carcinoma (median tumor diameter 1.4 cm; range 0.5–3.0 cm), a multicentric association was identified in one patient while a multifocal association was seen in two. One patient had nodal metastatic disease out of the ten who underwent axillary dissection. No lymphatic vessel invasion was identified in any tumors (P < 0.1 vs T1 IC). In addition, extensive intraductal spread was not present in any tumors (P < 0.05 vs T1 IC). This study shows that patients with pure tubular carcinoma are appropriate candidates for breast-conserving therapy based on the clinical/pathologic features. When a multifocal association is suspected preoperatively, either a wide local excision or a quadrantectomy which includes other lesions is thus recommended. Received: January 21, 2000 / Accepted: July 25, 2000     

95例乳腺癌保乳治疗近期观察

目的探讨乳腺癌保乳治疗的方法与疗效。方法95例Ⅰ-Ⅱ期原发性乳腺癌,施行局部扩大切除并腋窝淋巴结清扫,手术后患侧乳房接受放射治疗。结果手术后6个月随访,患者本人对保留乳房的满意率100％,十分满意者为92％。经随访2～51个月,平均随访17个月,仅1例同侧乳腺局部复发,2年局部复发率1．4％。无远处转移和死亡病例。结论Ⅰ-Ⅱ期乳腺癌实施保乳治疗,近期疗效满意,远期效果有待长期随访观察。     

Prognostic indicators following ipsilateral tumor recurrence in patients treated with breast-conserving therapy

Background

We attempt to determine significant predictors of systemic recurrence following ipsilateral breast tumor recurrence (IBTR).

Methods

A retrospective single-institution chart review of all newly diagnosed breast cancer patients was conducted to identify women treated with breast-conserving therapy (BCT) who developed IBTR. Charts were reviewed for demographics, clinical presentation, method of detection, stage, type of therapy, histopathology, and margin status for both the primary and recurrent tumors.

Results

Of 1,733 patients who were treated with BCT, 157 experienced IBTR. Multivariate Cox regression showed that time to recurrence and method of detection of local recurrence remained significant predictors of distant metastases-free survival (DMFS). Median DMFS times for clinically and radiographically detected IBTRs were 54 months and 231 months, respectively. Adjusted relative risk for clinically detected IBTRs was 2.2.

Conclusions

Given the prognostic significance of post-treatment mammography in our study, combined with median time to recurrence of 44 months, we believe that routine long-term mammographic surveillance is indicated following BCT.     

局部进展期及较大乳腺癌的保乳治疗

目的探讨局部进展期及较大乳腺癌的保乳问题。方法对33例肿瘤直径4．1cm以上的乳腺癌患者手术前予以蒽环类为主的联合化疗方案化疗,待肿瘤缩小后行保乳手术。结果33例患者中有3l例接受1～8周期的新辅助化疗,平均3．7个周期。化疗有效率100％,其中临床完全缓解19例,临床部分缓解12例,病理学完全缓解9例。33例保乳手术最终切缘阴性率100％,手术中切除标本切缘快速冰冻病理检查1次阴性率75．8％。全部病例随访2～39个月,中位随访27个月,无一例复发。结论对于局部进展期及较大肿瘤乳腺癌,采用以新辅助化疗为主的综合治疗,多数患者可以成功保乳,近期疗效与小肿瘤患者相近。