Molecular subtyping reveals uniqueness of prognosis in breast ductal carcinoma in situ patients with lumpectomy

BackgroundWe aimed to analyse the discrepancy in clinical features and prognosis between molecular subtypes in primary ductal carcinoma in situ (DCIS) patients with lumpectomy.MethodsPrimary DCIS patients were identified from the Surveillance, Epidemiology, and End Results registries database from 2010 to 2017. Based on immunohistochemistry markers of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2), enrolled DCIS cases were divided into four molecular subtypes, HR-HER2-, HR-HER2+, HR + HER2+, and HR + HER2-. Clinical features and prognosis were compared between molecular subtypes. Radiotherapy (RT) effects on prognosis were also analysed in each molecular subtype.ResultsA total of 5,628 DCIS cases were retrospectively enrolled in this study. HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- are 299 (5.3%), 498 (8.8%), 1,086 (19.3%), and 3,745 (66.5%), respectively. HR + HER2- cases have smaller tumor size (72.6%, P < 0.001) and lower grade (23.5%, P < 0.001). Comedo necrosis is more frequent in HR-HER2- (24.4%, P < 0.001) and HR-HER2+ DCIS cases (24.3%, P < 0.001). In univariate analyses, HR-HER2+ cases have significantly higher ipsilateral breast event (IBE) recurrence than HR+HER2- cases (P = 0.010). HR-HER2- cases show higher disease-specific mortality than HR+HER2+ cases (P = 0.021). In high-risk DCIS cases, RT reduces the absolute 5-year IBE incidence by 1.3%, 0.7%, 1.9%, and 2.6%, respectively in HR-HER2-, HR-HER2+, HR+HER2+, and HR+HER2- cases, respectively.ConclusionIn this population-based study, DCIS cases have diverse clinical and prognostic features for different molecular subtypes. Adjusting treatment strategies according to DCIS molecular subtypes is worth advancing.     

The evolution of the locoregional therapy of breast cancer

Breast-conserving therapy (BCT) and mastectomy have equal survival outcomes. Rates of local recurrence after BCT have declined steadily, largely as a result of the widespread use of systemic therapy. Sentinel node biopsy has replaced axillary dissection for staging the axilla, and in women undergoing BCT with whole-breast irradiation (WBI), axillary dissection is not needed for local control or survival in those with fewer than three involved sentinel nodes. Alternatives to 6 weeks of WBI have been shown to be safe and effective for subsets of breast cancer patients, and the use of preoperative chemotherapy allows BCT in some women who require mastectomy if surgery is the initial step in treatment. The combination of the smaller cancers detected with screening and the routine use of multimodality therapy has resulted in a decrease in the morbidity of local therapy and improved cancer treatment outcomes.     

The survival impact of the choice of surgical procedure after ipsilateral breast cancer recurrence

BACKGROUND: Many women with breast cancer recurrence previously treated with breast-conservation therapy desire repeat lumpectomies. We hypothesized that women undergoing mastectomy for breast cancer recurrence would show superior survival. METHODS: Patients who previously received breast-conservation therapy diagnosed with an ipsilateral breast cancer recurrence between 1988 and 2004 were identified using the Surveillance, Epidemiology, and End Results database. Univariate survival analysis was performed using the Kaplan-Meier method. Cox regression was used for multivariate analysis. RESULTS: Criteria for analysis were met in 747 patients. Of those, 24% underwent lumpectomy. On univariate analysis, patients undergoing lumpectomy had worse overall survival (P = .03). Five-year survival was 67% versus 78% for the lumpectomy and mastectomy groups, respectively. On multivariate analysis, mastectomy remained significantly associated with better survival with a hazard ratio of .5 (P = .003). CONCLUSIONS: The use of lumpectomy for ipsilateral breast cancer recurrence previously treated with breast-conservation therapy should generally be discouraged.     

Do additional shaved margins at the time of lumpectomy eliminate the need for re-excision?

Background

Most women diagnosed with breast cancer undergo breast-conservation surgery. Re-excision rates for positive margins have been reported to be greater than 50%. The purpose of our study was to determine if removing additional shaved margins from the lumpectomy cavity at the time of lumpectomy reduces re-excisions.

Methods

A retrospective study was performed on 125 women who had undergone lumpectomy with additional shaved margins taken from the lumpectomy cavity. Pathology reports were reviewed for tumor size and histology, lumpectomy and additional margin status, and specimen and margin volume.

Results

If additional margins were not taken, 66% would have required re-excision. Because of taking additional shaved margins, re-excision was eliminated in 48%.

Conclusion

Excising additional shaved margins at the original surgery reduced reoperations by 48%. There is a balance between removing additional margins and desirable cosmesis after breast-conservation surgery. The decision to take extra margins should be based on the surgeon's judgment.     

A novel ultrasound-guided electrosurgical loop device for intra-operative excision of breast lesions; an improvement in surgical technique

Background

The rate of involved margins after the excision of breast lesions using standard surgical techniques has historically ranged from approximately 20% to 45%. The localization and excision of breast lesions using intraoperative ultrasound has provided significant improvement. The authors report their collective experience with a novel technique utilizing the Phantom flexible loop electrosurgical device under ultrasound guidance for the intraoperative excision of breast lesions.

Methods

Seventy-nine breast lesions were excised using the Phantom device with intraoperative ultrasound. Rate of reexcision, excised specimen size, and size of the lumpectomy incision were reviewed.

Results

Fifty-nine of 79 lesions were malignant. Fifty-one (86.4%) had noninvolved final margins; 8 (13.6%) involved margins. The average specimen size was 21.3 cm³, compared with a range of 60 to 100 cm³ in the literature.

Conclusions

These results demonstrate improved efficiency, a decrease in the volume of excision, smaller incision size, and very low need for reoperation secondary to involved margins using the Phantom device for real-time, ultrasound-guided lumpectomy.     

Five-year results: the initial clinical trial of MammoSite balloon brachytherapy for partial breast irradiation in early-stage breast cancer

OBJECTIVE: Patients with early-stage invasive ductal breast cancer were prospectively evaluated using MammoSite RTS balloon brachytherapy (RTS Cytyc Corp, Marlborough, MA) as the sole modality for delivering accelerated partial breast irradiation to the lumpectomy bed with breast-conserving surgery. This report presents the 5-year results of the treated patients. METHODS: From May 2000 to October 2001, 70 patients were enrolled in this prospective study. Forty-three patients completed accelerated partial breast irradiation with MammoSite brachytherapy following lumpectomy and axillary staging. Thirty-six patients have been followed for a median of 5.5 years (mean 65.2 months). Criteria for entry into the study were unifocal invasive ductal carcinoma, tumor size < or = 2 cm, age > or = 45 years, absence of extensive intraductal component, cavity size > or = 3 cm in 1 dimension, node-negative, and final margins negative per National Surgical Adjuvant Breast and Bowel Project definition. A minimum balloon-to-skin surface distance of 5 mm was required. A dose of 34 Gy was delivered in 10 fractions over 5 days prescribed to 1 cm from the applicator surface using iridium-192 high-dose-rate brachytherapy. Data on infection, seromas, cosmetic outcome, and toxicities were collected at 3 and 6 months and at yearly intervals. Local recurrences, both true recurrences in the lumpectomy bed and failures outside the initially treated target volume (elsewhere failures), were recorded. Contralateral breast failure rates were noted. RESULTS: The catheter was not implanted in 16 of the 70 enrolled patients due to cavity size not amenable to balloon placement (n = 10), ineligible by criteria (n = 4), and skin spacing (n = 2). Fifty-four patients were implanted and 43 were successfully treated with MammoSite balloon brachytherapy. Reasons for catheter explantation in 11 patients were poor cavity conformance in 7, inadequate skin spacing in 2, positive node in 1 and age less than 45 years in 1. Of the 43 patients who completed treatment, the infection rate was 9.3%. Seroma formation occurred in 32.6% of patients, of which 12% were symptomatic requiring aspiration. Asymptomatic fat necrosis was identified in 4 of the 43 patients, noted from time of catheter removal at 11, 14, 42, and 63 months. Good-excellent cosmetic outcomes were achieved in 83.3% of the 36 patients with more than 5 years of follow-up. Cosmetic outcomes were improved, with increased skin spacing having statistical significance at skin spacing > or = 7 mm. The only serious adverse events were 2 infections: mastitis and abscess. Seven of the 43 treated patients have been discontinued from follow-up. None had a local recurrence recorded at last visit. Reasons for exit from the study were death from metastatic disease (n = 3), lost to follow-up (n = 2), and placed in hospice for other medical conditions (n = 2). No local recurrences (either at the tumor bed or elsewhere in the breast) or regional recurrences have occurred in the 36 patients who have been followed for a median of 5.5 years. No contralateral cancers have developed. CONCLUSIONS: MammoSite balloon brachytherapy as a sole modality for delivering radiation to the tumor bed has been successful in achieving excellent local control in this initial clinical study of patients with early-stage invasive ductal breast cancer. This has been achieved with minimal toxicities and good-excellent cosmetic outcomes in 83.3%. Accelerated partial breast irradiation using the MammoSite balloon in a carefully selected group of patients has demonstrated 5-year local recurrence results comparable to those achieved with conventional whole breast radiation therapy and interstitial catheter brachytherapy as reported at 5-year data points in studies of these treatment modalities. Poor cavity conformance and inadequate skin distance were the main factors limiting use of the MammoSite device. Extended follow-up will be required to determine the long-term efficacy of this treatment modality.     

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.     

Factors Associated with Negative Margins of Lumpectomy Specimen: Potential Use in Selecting Patients for Intraoperative Radiotherapy

Background Lumpectomy followed by radiation is standard treatment for early breast cancer. Recently, the use of partial breast intraoperative radiation (IORT) has been developed, and patients selected for IORT should not have positive margins. This study’s purpose was to identify factors predicting negative margins after lumpectomy. Methods Patient age, preoperative investigations, surgery, final pathology, and margin status were examined using a prospective database between 1999 and 2005. Univariate and multivariate logistic regression analysis were performed to identify patient and tumor factors predicting an increased rate of negative margins. The results were used to generate a patient selection algorithm. Results The rate of positive margins at first resection was 17% in 730 lumpectomies (708 patients). Multivariate analysis revealed that older age (P = .0006), smaller tumor size (P < .0025), type of surgery (OR = 3.4 for ultrasound vs mammogram-guided wire localization, P = .003), and having a core needle biopsy (CNB) with preoperative cancer diagnosis (P < .0001) were predictive for having a negative margin. Patients older than age 50 with a preoperative CNB showing invasive cancer less that 3 cm that can be localized under ultrasound had a negative margin rate of 98 % (n = 178). These patients would be ideal for consideration of IORT. Conclusions Negative margin rates after lumpectomy are predicted by age, tumor size, preoperative investigations, and localization technique. These variables can be used to select patients for IORT with a 2.2% chance of positive margins. Presented at the 13th Annual Meeting of the Canadian Society of Surgical Oncology, Toronto, Ontario, Canada, April 27, 2007.     

Ablación por radiofrecuencia del lecho quirúrgico tras tumorectomía en cirugía conservadora del cáncer de mama

IntroductionObtaining tumor-free margins during breast conservative surgery (BCS) is essential to avoid local recurrence and frequently requires reoperation. Radiofrequency ablation (RFA) of surgical margins after lumpectomy seems to be a helpful tool to avoid reoperations, but evidence is insufficient. This study analyzes the efficacy and safety of RFA after BCS to obtain free surgical margins.MethodsNon-randomized experimental study performed in an intervention group of 40 patients assigned to receive RFA after lumpectomy and successive resection of surgical margins, and a historical control group of 40 patients treated with BCS alone. In the intervention group, the RFA effect on tumor cell viability in the surgical margins was analyzed. Also, reoperation rate, complications and cosmetic results were compared in both groups.ResultsA total of 240 excised margins were analyzed after RFA, obtaining a high number of tumor-free margins. Compared to the control group, the reoperation rate decreased significantly (0% vs 12%; P = .02), without differences in terms of postoperative complications (10% vs 5%; P = .67) or cosmetic results (excellent or good 92.5% vs 95%; P = .3).ConclusionsRFA after lumpectomy is a reliable, safe and successful procedure to obtain tumor-free surgical margins and to decrease the reoperation rate without affecting complications or compromising cosmetic results.     

Ductal Carcinoma In Situ of the Breast

Ductal carcinoma in situ (DCIS) of the breast is a potentially invasive neoplasm. Risk factors include high estrogen states such as use of oral contraceptive (OC) pills, nulliparity, advanced age at first birth, and also family history and genetic mutations. The incidence of this usually clinically silent condition has risen in the past few decades due to widespread screening and diagnostic mammography, with final diagnosis confirmed by biopsy. At present, treatment options include total or simple mastectomy or lumpectomy with radiation. Adjuvant therapy includes antiestrogens like tamoxifen and human epidermal growth factor receptor 2 (HER2) suppression therapy. With the latest advances in chemotherapy and better understanding on the pathogenesis of the lesion, it is anticipated that more effective modalities of treatment may soon be available.