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.     

Assessment of treatment for patients with primary ductal carcinoma in situ in the breast

Background: Current mammographic technology has resulted in increased detection of ductal carcinoma in situ (DCIS). It is necessary to assess which patients presenting with DCIS are good candidates for breast conservation and which of these patients should receive adjuvant radiation. Methods: We accrued clinical data for 124 patients with a primary diagnosis of DCIS from 1979 through 1994. Primary therapy was a mastectomy for 18 patients, and a lumpectomy for 106 patients. Only 18 of the latter group of patients received adjuvant radiotherapy. For the 88 lumpectomy-alone patients (median follow-up, 5.2 years), we evaluated the effects of clinical (age and initial presentation) and pathologic (nuclear grade, architecture, parenchymal involvement, calcifications, and measured margins) factors on recurrence of DCIS or the development of invasive breast cancer. Results: Patients who underwent lumpectomy with or without adjuvant radiotherapy (median follow-up, 5.0 years) were significantly more likely to have recurrence of DCIS (P=.05) than those who underwent mastectomy (median follow-up, 6.7 years): 18% (19/106) versus 0% (0/18), respectively; lumpectomy-alone patients experienced a 19% (17/88) rate of DCIS recurrence. All recurrent DCIS was ipsilateral. For lumpectomy-alone patients, the factors associated with ipsilateral recurrence of DCIS were extent of involvement of the parenchyma (P=.01, for univariate;P=.07, for multivariate) and initial presentation (P=.05, for univariate;P=.07, for multivariate). Eleven lumpectomy-alone patients developed invasive breast cancer (6 ipsilateral, 5 contralateral); none of the 18 lumpectomy patients who received adjuvant radiation developed invasive disease. None of the factors investigated, including primary surgery and adjuvant radiotherapy, were associated with a significant effect on the development of invasive disease. Conclusions: Longer follow-up is required to determine if the benefits of either mastectomy or radiotherapy following lumpectomy persist. There is a suggestion that patients under 40 years of age or women who present with nipple discharge might be considered for either adjuvant radiotherapy following lumpectomy or a simple mastectomy.     

早期乳腺癌肿瘤切除联合放射治疗12年随访结果

目的总结早期乳腺癌肿瘤切除联合放射治疗的12年随访结果. 方法 1988年11月～1990年6月,对31例早期乳腺癌施行肿瘤切除联合放疗(肿瘤切除组),35例施行改良根治术(改良根治组),比较2组病人术后12年复发率和生存率. 结果肿瘤切除组局部复发率6.5%(2/31),总生存率74.1%;改良根治组复发率2.9%(1/35),生存率为74.3%.2组的复发率及总生存率均无显著性差别(Logrank检验, χ2=1.04,P＞0.05; χ2=0.55,P>0.05). 结论对于早期乳腺癌,行肿瘤切除联合放疗是一种安全、可行的方法.     

Malignant phyllodes tumor of the breast: local control rates with surgery alone

PURPOSE: Patients with malignant phyllodes tumors of the breast (MPTB) are routinely treated with surgery alone. We performed a retrospective study to determine local control rates based on tumor size and type of surgery performed. METHODS AND MATERIALS: We reviewed records of 478 patients with MPTB treated between March 1964, and August 2005. The data were extracted from the IMPAC National Oncology Database consisting of merged tumor registries from 130 hospitals. RESULTS: Median follow-up was 64 months (range, 0-410 months). Actuarial 5-year local control rates were 79.4% for 169 lumpectomy patients and 91.2% for 207 mastectomy patients treated by surgery alone. Five-year local control rates for lumpectomy based on tumor size were 91% for 0-2 cm tumors, 85% for 2-5 cm tumors, and 59% for 5-10 cm tumors. For mastectomy patients, 5-year local control rates were 100% for 0-2 cm tumors, 95% for 2-5 cm tumors, 88% for 5-10 cm tumors, and 85% for 10-20 cm tumors. Multivariate analysis of overall survival found several factors to be significant including advancing age with each decade after 50 years of age, appearance of distant metastases, larger primary tumor size, and local control vs. local recurrence (Hazard Ratio [HR] 2.5, p < 0.05). CONCLUSIONS: Malignant phyllodes tumors of the breast local recurrence rates are 15% or greater for patients with tumors >2 cm treated by lumpectomy alone and tumors >10 cm treated by mastectomy alone. Adjuvant radiation therapy should be evaluated for these patients. This may be especially important because our study showed that local recurrence impacted on survival rates.     

保乳术前肿瘤MRI体积与术后标本体积及基于金属夹勾画术腔体积比较研究

目的 探讨保乳患者术前MRI肿瘤体积与术后标本测量体积及基于金属夹勾画的瘤床体积间的差异性与相关性.方法 2014—2015年间50例乳腺癌保乳患者入组.基于术前MRI勾画GTV并定义为GTVMRI,其边界外扩1.0 cm得到GTVMRI+1.测量切除标本体积并测量和计算病理体积,分别定义为GTVES和GTVPAT.在定位CT图像上基于术腔边界金属夹勾画GTV,并定义为GTVTB.Friedman检验,Wilcoxon法两两比较,Spearman等级相关分析.结果 GTVMRI、GTVMRI+1、GTVPAT、GTVES、GTVTB中位数(范围)分别为0.97(0.01~6.88)、12.58(3.90~34.13)、0.97(0.01~2.36)、15.46(1.15~70.69)、19.24(4.72~54.33)cm3.GTVMRI与GTVPAT、GTVMRI+1与GTVES、GTVTB与GTVES差异均无统计学意义(P=0.188、0.07、0.264).GTVTB、GTVES与GTVMRI均无相关性(P=0.378、0.071),GTVTB、GTVES与GTVMRI+1也均无相关性(P=0.375、0.068),而GTVTB与GTVES呈正相关(r=0.488,P=0.004).结论 在非影像引导情况下,保乳治疗的患者基于触诊范围行局部肿瘤切除术时,切除标本体积及基于金属夹勾画的术腔体积与基于术前MRI图像所勾画与构建的肿瘤体积均无相关性.     

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.     

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.     

Acute Toxicity of High-Dose-Rate Intracavitary Brachytherapy With the MammoSite Applicator in Patients With Early-Stage Breast Cancer

Background: Intracavitary brachytherapy with the MammoSite applicator as the sole radiation treatment in breast-conserving therapy is an option for women with early-stage breast cancer; we evaluated the acute toxicities associated with this treatment method.Methods: Thirty-one patients with 32 stage I or II breast carcinomas underwent breast-conserving therapy, which included lumpectomy with negative margins, sentinel node biopsy, or axillary dissection, followed by brachytherapy with the MammoSite applicator. Acute radiation skin complications were graded on the day of radiotherapy completion and at weeks 2, 4, 6, and 12 after radiation treatment. Cosmesis was graded on the Harvard Scale at all follow-ups.Results: The median follow-up was 11 months (range, 4–15 months). Twenty-seven of the 31 patients were treated with the device as the sole method of radiotherapy. No acute toxicities occurred during the 5 days of treatment. Nineteen patients (68%) had no to mild acute skin reactions, and 25% developed bright erythema and patchy moist desquamation. Two patients (7%) developed confluent moist desquamation within the first 4 weeks (grade 3); this healed by week 12. All skin reactions were localized to the area overlying the balloon. Sixteen percent (5 of 32) of all breasts with implants developed infection. Cosmesis was good to excellent in 86% of cases.Conclusions: Most acute skin toxicities were mild. Our infection rate was higher than in prior studies that used interstitial brachytherapy. Cosmesis was good to excellent in most patients. Breast brachytherapy with the MammoSite catheter was well tolerated; further investigations of breast brachytherapy with this system are warranted.     

Avoidance of Adjuvant Radiotherapy in Selected Patients With Invasive Breast Cancer

Background: Current standard therapy for invasive breast carcinoma is mastectomy or breast conservation with adjuvant radiation. Data from randomized trials suggest no advantage for radiotherapy after lumpectomy in highly selected patients. Selective radiotherapy would make contemporary breast cancer therapy more rational with decreased morbidity and expense.Methods: A total of 163 patients were treated by breast conservation without adjuvant radiation between 1978 and June 2003. They declined radiation after discussion or had medical contraindications. The great majority were postmenopausal and had lower-grade T1 tumors with resection margins 1 cm and no nodal metastases. The goal was to identify patients with favorable prognostic features for omission of postsurgical irradiation without impaired local recurrence or survival.Results: Twenty patients (12%) had local recurrences; 17 (10%) were invasive, and 3 (2%) were ductal carcinoma-in-situ. An ideal patient subgroup >50 years of age with grade 1 or 2 cancers 1.5 cm in diameter and with surgical margins 1 cm was empirically defined. Of 80 such patients, 5 (6%) had local recurrence; 3 (3.5%) were invasive, and 2 (2.5%) were ductal carcinoma-in-situ.Conclusions: A defined ideal subset of older breast cancer patients with smaller, lower-grade cancers and adequate excision margins can be treated with lumpectomy without irradiation and with minimal local recurrence.