Local treatment options for young women with ductal carcinoma in situ: A systematic review and meta-analysis comparing breast conserving surgery with or without adjuvant radiotherapy,and mastectomy

PurposeYoung age is associated with poor prognosis in ductal carcinoma in situ (DCIS) of female breast and controversy exists regarding the optimal treatment modality for young patients. We aimed to compare treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy (BCS + RT), and total mastectomy (MT) for young DCIS women.MethodsPubMed, Cochrane, and Embase were searched for studies reporting comparative results among BCS, BCS + RT, or MT in ≤50 years old (y/o) DCIS females. Study quality was assessed and meta-analysis with subgroup analysis was performed to pool the effect sizes of the outcomes-of-interest.ResultsWe included 3 randomized control trials and 18 observational studies. For DCIS women ≤50 y/o, RT following BCS significantly reduced the risk for ipsilateral breast tumor recurrence (IBTR) (HR = 0.66, 95% CI 0.50–0.87). However, the benefit was less robust in extremely young patients and with long follow-ups. RT revealed no statistically significant preventive effect on ipsilateral invasive recurrence (HR = 1.38, 95% CI 0.98–1.94). On the other hand, MT yielded the lowest IBTR (BCS + RT vs MT: HR = 4.4, 95% CI 2.06–9.40), both in ipsilateral DCIS recurrence and ipsilateral invasive recurrence. There was great heterogeneity and could not reach an evident conclusion concerning survival outcomes.ConclusionThis study highlighted the varying effect of RT for young DCIS females. The local control benefit of MT was definite without survival differences observed. Our study provided a moderate certainty of evidence to guide the treatment for young DCIS women. Further age-specific prospective trial is warranted.     

Selective use of whole breast radiotherapy after breast conserving surgery for invasive breast cancer and DCIS

BackgroundRadiotherapy following breast conservation is routine in the treatment of invasive breast cancer and is commonly used in ductal carcinoma in situ to decrease local recurrence. However, adjuvant breast radiotherapy has significant short and longer-term side effects and consumes substantial health care resources. We aimed to review the randomised controlled trials and attempted to identify clinico-pathological factors and molecular markers associated with the risk of local recurrence.MethodsA literature search using the Medline and Ovid databases between 1965 and 2011 was conducted using the terms ‘breast conservation’ and radiotherapy, and radiotherapy and DCIS. Only papers with randomised clinical trials published in English in adult were included. Only Level 2 evidence and above was included.ResultsThree meta-analyses and 17 randomised controlled trials have been published in invasive disease and one meta-analysis and four randomised controlled trials for DCIS. Overall, adjuvant radiotherapy provides a 15.7% decrease in local recurrence and 3.8% decrease in 15-year risk of breast cancer death. The key clinico-pathological factors, which enable stratification into high, intermediate or low risk groups include age, oestrogen receptor positivity, use of tamoxifen and extent of surgery. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories are 7.8%, 1·1%, and 0·1% respectively Adjuvant radiotherapy provides a 60% risk reduction in local recurrence in DCIS with no impact on distal metastases or overall survival. Size, pathological subtype and margins are major risk factors for local recurrence in DCIS.ConclusionsAdjuvant radiotherapy consistently decreases local recurrence across all subtypes of invasive and in-situ disease. While it has a survival advantage in those with invasive disease, this is not seen with DCIS and is minimal in invasive disease where the risk of local recurrence is low. This group includes women over 70 with node negative, ER positive tumours<2 cm.     

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.     

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.     

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.     

Patterns of care analysis among women with ductal carcinoma in situ in North Carolina

BACKGROUND: Ductal carcinoma in situ (DCIS) of the breast comprises approximately 25% of new breast cancer cases. The aim of this study was to delineate patterns of care for women with DCIS as related to age, tumor characteristics, and race/ethnicity. Further study goals included the identification of predictors of breast-conserving surgery (BCS), adjuvant radiation, and/or hormonal therapy, as well as breast reconstruction after mastectomy. METHODS: The North Carolina Cancer Registry was queried for primary DCIS treated in 1998 and 1999 (n = 1,893). Logistic regression analysis was performed to define the determinants of patterns of care. RESULTS: Thirty-five percent of the women in this study sample underwent mastectomy. Positive predictors of mastectomy included young age (age <50 y vs 70+; odds ratio [OR], 1.55; 95% confidence interval [CI], 1.13-2.11) and larger tumor size (>2 mm vs 0-1 mm; OR, 2.43; 95% CI, 1.63-3.60). Approximately 48% of women who underwent BCS received adjuvant radiation therapy. Factors associated with receiving radiation therapy after BCS include younger age (age <50 vs 70+; OR, 2.12; 95% CI, 1.49-3.03). Approximately 19% of women who underwent BCS received adjuvant hormonal therapy. Positive predictors of receiving adjuvant hormonal therapy after BCS included age of 50 to 60 years versus 70+ (OR, 2.16; 95% CI, 1.36-3.44) and the receipt of radiation therapy (OR, 3.60; 95% CI, 2.55-5.06). Approximately 28% of women who underwent mastectomy received breast reconstruction surgery. Positive predictors of breast reconstruction after mastectomy included age younger than 50 years versus 70+ years (OR, 47.36; 95% CI, 19.45-115.32). African American race was associated negatively with receipt of breast reconstruction after mastectomy (OR, .46; 95% CI, .26-.84). CONCLUSIONS: Treatment strategies for primary surgical therapy for DCIS vary significantly by age. Inconsistencies exist surrounding the use of adjuvant radiation therapy after BCS in women with DCIS. Variations in approaches to reconstructive surgery after mastectomy may be related to age, ethnicity, and/or economic constraints.     

Local recurrence outcomes after breast conserving surgery and adjuvant radiotherapy in ductal carcinoma in situ of the breast and a comparison with ECOG E5194 study

PurposeTurkish Radiation Oncology Study Group investigated local recurrence rates and prognostic factors in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conservative surgery (BCS) followed by radiotherapy (RT) and Eastern Cooperative Oncology Group (ECOG) Study E5194 were compared with the original study.Patients and methodsTotally 252 patients were evaluated retrospectively. Prognostic factors that might influence local control (age, nuclear grade, comedo necrosis, surgical margins, tumor size, hormone receptor status) were compared. The eligibility criteria of ECOG 5194 were stratified into two groups as in the original study and were compared for local control.ResultsThe median follow-up time was 59 (21–220) months. Local recurrence was observed in 9 patients (3.6%) who had invasive carcinoma (3 patients) and DCIS (6 patients). Ten years local control rates was 91.8% respectively. We found that the risk of ipsilateral breast recurrence was significantly higher in women younger than 50 years old (p = 0.016). In addition, a statistically significant trend was found in patients with tumor larger than 1 cm and HER2 positive tumors (p = 0.051, p = 0.068 respectively). When 12-year results were compared with the ECOG 5194, adjuvant RT produced an absolute difference of 11% in low-intermediate and 20% in high grade in local control.ConclusionIn our study, the 10-year local control rate was 92% and younger than 50 years old was the most important unfavorable prognostic factor for local recurrence. There was provided 20% absolute local control with adjuvant radiotherapy which eligibility criteria of ECOG 5194 high grade group.     

A review of the management of ductal carcinoma in situ following breast conserving surgery

Ductal carcinoma in situ (DCIS) is a heterogeneous, pre-malignant disease accounting for 10–20% of all new breast tumours. Evidence shows a statistically significant local control benefit for adjuvant radiotherapy (RT) following breast conserving surgery (BCS) for all patients. The baseline recurrence risk of individual patients varies according to clinical-pathological criteria and in selected patients, omission of RT may be considered, following a discussion with the patient. The role of adjuvant endocrine therapy remains uncertain. Ongoing studies are attempting to define subgroups of patients who are at sufficiently low risk of recurrence that RT may be safely omitted; investigating RT techniques and dose fractionation schedules; and defining the role of endocrine therapy. Future directions in the management of patients with DCIS will include investigation of prognostic and predictive biomarkers to inform individualised therapy tailored to the risk of recurrence.     

HER-2 overexpression is not associated with increased ipsilateral breast tumor recurrence in DCIS treated with breast-conserving surgery followed by radiotherapy

BackgroundWe evaluated the clinical implications of human epidermal growth factor receptor (HER)-2 overexpression after adjuvant radiotherapy (RT) for ductal carcinoma in situ (DCIS).MethodsWe reviewed 215 patients with DCIS who underwent breast-conserving surgery followed by RT. The association between HER-2 overexpression and ipsilateral breast tumor recurrence (IBTR) was evaluated.ResultsHER-2 overexpression was associated with comedo-type architecture, high nuclear grade, and negative hormonal receptors. The median follow-up duration was 75 months. Sixteen patients experienced IBTR; seven as DCIS recurrence and nine as invasive recurrence. The IBTR rate was 11.4% at 10 years. There was no significant difference in IBTR according to HER-2 expression (P = 0.1764), neither in invasive nor DCIS recurrence. Time to recurrence was shorter in HER-2 positive tumors (P = 0.0697).ConclusionAdjuvant RT seems to counteract the negative effect of HER-2 overexpression in DCIS, while time to recurrence was relatively shorter.     

Targeted Intraoperative Radiotherapy for the Management of Ductal Carcinoma In Situ of the Breast

Multiple long‐term studies have demonstrated a propensity for breast cancer recurrences to develop near the site of the original breast cancer. Recognition of this local recurrence pattern laid the foundation for the development of accelerated partial breast irradiation (APBI) approaches designed to limit the radiation treatment field to the site of the malignancy. However, there is a paucity of data regarding the efficacy of APBI in general, and intraoperative radiotherapy (IORT), in particular, for the management of ductal carcinoma in situ (DCIS). As a result, use of APBI, remains controversial. A prospective nonrandomized trial was designed to determine if patients with pure DCIS considered eligible for concurrent IORT based on preoperative mammography and contrast‐enhanced magnetic resonance imaging (CE‐MRI) could be successfully treated using IORT with minimal need for additional therapy due to inadequate surgical margins or excessive tumor size. Between November 2007 and June 2014, 35 women underwent bilateral digital mammography and bilateral breast CE‐MRI prior to selection for IORT. Patients were deemed eligible for IORT if their lesion was ≤4 cm in maximal diameter on both digital mammography and CE‐MRI, pure DCIS on minimally invasive breast biopsy or wide local excision, and considered resectable with clear surgical margins using breast‐conserving surgery (BCS). Postoperatively, the DCIS lesion size determined by imaging was compared with lesion size and surgical margin status obtained from the surgical pathology specimen. Thirty‐five patients completed IORT. Median patient age was 57 years (range 42–79 years) and median histologic lesion size was 15.6 mm (2–40 mm). No invasive cancer was identified. In more than half of the patients in our study (57.1%), MRI failed to detect a corresponding lesion. Nonetheless, 30 patients met criteria for negative margins (i.e., margins ≥2 mm) whereas five patients had positive margins (<2 mm). Two of the five patients with positive margins underwent mastectomy due to extensive imaging‐occult DCIS. Three of the five patients with positive margins underwent successful re‐excision at a subsequent operation prior to subsequent whole breast irradiation. A total of 14.3% (5/35) of patients required some form of additional therapy. At 36 months median follow‐up (range of 2–83 months, average 42 months), only two patients experienced local recurrences of cancer (DCIS only), yielding a 5.7% local recurrence rate. No deaths or distant recurrences were observed. Imaging‐occult DCIS is a challenge for IORT, as it is for all forms of breast‐conserving therapy. Nonetheless, 91.4% of patients with DCIS were successfully managed with BCS and IORT alone, with relatively few patients requiring additional therapy.     

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.     

Local and national trends over a decade in the surgical treatment of ductal carcinoma in situ

BACKGROUND: Ductal cancer in situ (DCIS) is an increasingly frequent diagnosis in breast cancer, and management continues to challenge surgeons and oncologists. The purpose of our study was to examine local and national rates of breast conservation surgery and breast reconstruction surgery and to explore patient and surgeon factors associated with the procedures. METHODS: Review of the 1,342 patients in our institutional breast cancer database yielded 211 patients with DCIS. The sample of 211 patients was compared with a national (Nationwide Inpatient Sample [NIS]) database. Patient and surgeon factors associated with the use of breast conservative surgery (BCS) and breast reconstruction (BR) postmastectomy were identified. RESULTS: At our institution, the use of BCS steadily increased over ten years. Younger women with nonpalpable tumors, nonprivate insurance, and younger surgeons were more likely to have BCS. In 28 patients, breast reconstruction was performed: younger Caucasian women with private insurance and younger surgeons were more likely to undergo reconstruction. NIS data revealed that BCS was performed in 20% but that BCS did not increase over the 12-year period. CONCLUSIONS: There was a steady increase in the use of BCS for DCIS at our institution, but a consistent, and much lower, use nationally. To increase breast conservation and reconstruction for DCIS, educational efforts should especially be directed toward elderly women and elderly surgeons.     

Imaging of lumpectomy surface with large field-of-view confocal laser scanning microscope for intraoperative margin assessment - POLARHIS study

IntroductionBreast-conserving surgery (BCS) in case of breast cancer and/or in-situ-carcinoma lesions (DCIS) intends to completely remove breast cancer while saving healthy tissue as much as possible to achieve better aesthetic and psychological outcomes for the patient. Such modality should result in postoperative tumor-free margins of the surgical resection in order to carry on with the next therapeutical steps of the patient care. However, 10–40% of patients undergo more than one procedure to achieve acceptable cancer-negative margins. A 2nd operation or further operation (re-operation) has physical, psychological, and economic consequences. It also delays the administration of adjuvant therapy, and has been associated with an elevated risk of local and distant disease relapse. In addition, a high re-operation rate can have significant economic effects - both for the service provider and for the payer. A more efficient intraoperative assessment of the margin may address these issues. Recently, a large field-of-view confocal laser scanning microscope designed to allow real-time intraoperative margin assessment has arrived on the market - the Histolog Scanner. In this paper, we present the first evaluation of lumpectomy margins assessment with this new device.Materials and methods40 consecutive patients undergoing BCS with invasive and/or DCIS were included. The whole surface of the surgical specimens was imaged right after the operation using the Histolog Scanner (HLS). The assessment of all the specimen margins was performed intraoperatively according to the standard-of-care of the center which consists of combined ultrasound (IOUS) and/or conventional specimen radiography (CSR), and gross surgical inspection. Margin assessment on HLS images was blindly performed after the surgery by 5 surgeons and one pathologist. The capabilities to correctly determine margin status in HLS images was compared to the final histopathological assessment. Furthermore, the potential reduction of positive-margin and re-operation rates by utilization of the HLS were extrapolated.ResultsThe study population included 7/40 patients with DCIS (17.5%), 17/40 patients with DCIS and invasive ductal cancer (IDC NST) (42.5%), 10/40 patients with IDC NST (25%), 4/40 with invasive lobular cancer (ILC) (10%), and 1/40 patients with a mix of IDC NST, DCIS, and ILC. Clinical routine resulted in 13 patients with positive margins identified by final histopathological assessment, resulting in 12 re-operations (30% re-operation rate). Amongst these 12 patients, 10 had DCIS components involved in their margin, confirming the importance of improving the detection accuracy of this specific lesion. Surgeons, who were given a short familiarization on HLS images, and a pathologist were able to detect positive margins in 4/12 and 7/12 patients (33% and 58%), respectively, that were missed by the intraoperative standard of care. In addition, a retrospective analysis of the HLS images revealed that cancer lesions can be identified in 9/12 (75%) patients with positive margins.ConclusionThe present study presents that breast cancer can be detected by surgeons and pathologists in HLS images of lumpectomy margins leading to a potential reduction of 30% and 75% of the re-operations. The Histolog Scanner is easily inserted into the clinical workflow and has the potential to improve the intraoperative standard-of-care for the assessment of breast conserving treatments. In addition, it has the potential to increase oncological safety and cosmetics by avoiding subsequent resections and can also have a significant positive economic effect for service providers and cost bearers. The data presented in this study will have to be further confirmed in a prospective phase–III–trial.     

Multiple re-excisions versus mastectomy in patients with persistent residual disease following breast conservation surgery

BACKGROUND: Persistently involved margins following breast conservation surgery (BCS) create a diagnostic dilemma regarding the recommendation of further BCS or mastectomy. METHODS: A retrospective review of 276 breast cancer patients who underwent BCS and required additional surgical treatment between 1990-2002 was performed. RESULTS: For treatment of persistently involved margins, 63% of subjects underwent re-excision the first time, 49% the second time, and 37% the third time. The incidence of residual carcinoma increased linearly with the number of initially involved margins (P = .03). Ductal carcinoma-in-situ (DCIS) or infiltrating lobular carcinoma (IFLC) primary histology was associated with a higher rate of residual cancer compared to invasive ductal carcinoma (IFDC) (62% vs. 69% vs. 54%, respectively, P = .56). A trend towards an increased risk of residual cancer in primary tumors > or =2 cm versus tumors under 2 cm was also evident (63%% vs. 50%, respectively, P = .38). CONCLUSIONS: Approximately half of patients repeatedly selected BCS over mastectomy. It is important to realistically discuss the probability of definitive resection with patients who are undergoing breast conservation with re-excision.     

Surgical margins and risk of locoregional recurrence in invasive breast cancer: An analysis of 10-year data from the Breast Cancer Treatment Quality Assurance Project

AimThere is debate as to what constitutes an adequate excision margin to reduce the risk of locoregional recurrence (LRR) after breast cancer surgery. We have investigated the relationship between surgical margin distance and LRR in women with invasive breast cancer (IBC).MethodsTumour free margin distances were extracted from histopathology reports for women with IBC, treated by either breast conserving surgery or mastectomy, enrolled in the Breast Cancer Treatment Group Quality Assurance Project from July 1997 to June 2007. Cox proportional hazards regression analyses were conducted to compare the risk of LRR for involved margins compared with negative margins, measured in increments rounded to the nearest mm.Results88 of 2300 patients (3.8%) experienced an LRR after a mean follow-up of 7.9 years. An involved margin, or a margin of 1 mm was associated with an increased risk of LRR (HR 2.72, 95% CI 1.30–5.69), whilst margin distances of 2 mm or greater were not. Risk of LRR with margin distances <2 mm was particularly high amongst those not receiving radiotherapy (RT).ConclusionBased on our findings, we recommend that a tumour free margin distance of 2 mm be adopted as an adequate margin of excision for IBC, in the setting of patients receiving standard adjuvant RT and adjuvant drug therapies as dictated by the current clinical treatment paradigms.     

Is the systematic circumferential tumor cavity shaving a representative sample for the remaining mammary gland? About 75 cases

IntroductionThe conservative surgery is more and more indicated for breast cancer. However, we still fear local recurrence which is mostly due to residual tumors?. Several techniques have been used to minimize theses residual tumors; one of them is the systematic circumferential tumor cavity shaving (SCTCS).MethodsWe sampled 75 female patients who had conservative surgery with positive shaved margins in the anatomopathology examination and to whom a complementary treatment with mastectomy have been decided.ResultsThe median age was 48 years old. The median tumor size was 23 mm. In the histological examination of the tumors, 93% were invasive ductal carcinoma associated in 50% of the cases to the presence of ductal carcinoma in situ (DCIS) where all the lumpectomies had clear margin. For the SCTCS, 62,2% were DCIS and in 17,6% of the cases were invasive ductal carcinoma. A complementary treatment with mastectomy was indicated to all the patients. A residual tumor was detected in the remaining mammary gland in 47,7% of the cases out of which 50% were DCIS. Local recurrence happened in three patients (4,6%) after a median of follow up of 36 months. The overall survival and the disease free survival at five years were respectively 83,6% and 75,5%.ConclusionStandardized lumpectomy cavity shaving provides a backup to lumpectomy margins in conservative breast surgery but it can also be used as a sample for the remaining breast, helping to detect the residual tumor, and decreasing the rates of local recurrence after BCT.     

Breast conservative surgery for well-differentiated ductal intraepithelial neoplasia: Risk factors for ipsilateral breast tumor recurrence

RationalWe retrospectively analyzed 232 patients affected by well differentiated ductal intraepithelial neoplasia (DIN1c or DCIS G1) treated with conservative surgery without adjuvant radiotherapy.Results25 invasive and 18 non-invasive local recurrences were observed (median follow-up 80 months; 5-year cumulative incidence: 12.2%). Seven of the 15 young patients (<40 y) developed local recurrence (2 in situ, 5 invasive). Age <50 (HR 1.89, 95% C.I. 1.01–3.45), multifocality (HR 3.21, 95% C.I. 1.46–7.06), Ki-67 > 7% (HR 2.33, 95% C.I. 1.20–4.55) and surgical margins <10 mm (HR 2.00, 95% C.I. 1.06–3.76) were significantly associated with an increased risk of local recurrence.ConclusionsYoung age, multifocality and small margins appeared as clear risk factors of local recurrence in DIN1c (DCIS G1) population. The presence of multiple poor prognostic features warrant a thorough discussion regarding local treatment.     

Risk factors for estrogen receptor positive ductal carcinoma in situ of the breast in African American women

BackgroundCompared to U.S. white women, African American women are more likely to die from ductal carcinoma in situ (DCIS). Elucidation of risk factors for DCIS in African American women may provide opportunities for risk reduction.MethodsWe used data from three epidemiologic studies in the African American Breast Cancer Epidemiology and Risk Consortium to study risk factors for estrogen receptor (ER) positive DCIS (488 cases; 13,830 controls). Results were compared to associations observed for ER+ invasive breast cancer (n = 2,099).ResultsFirst degree family history of breast cancer was associated with increased risk of ER+ DCIS [odds ratio (OR): 1.69, 95% confidence interval (CI): 1.31, 2.17]. Oral contraceptive use within the past 10 years (vs. never) was also associated with increased risk (OR: 1.43, 95%CI: 1.03, 1.97), as was late age at first birth (≥25 years vs. <20 years) (OR: 1.26, 95%CI: 0.96, 1.67). Risk was reduced in women with older age at menarche (≥15 years vs. <11 years) (OR: 0.62, 95%CI: 0.42, 0.93) and higher body mass index (BMI) in early adulthood (≥25 vs. <20 kg/m² at age 18 or 21) (OR: 0.75, 95%CI: 0.55, 1.01). There was a positive association of recent BMI with risk in postmenopausal women only. In general, associations of risk factors for ER+ DCIS were similar in magnitude and direction to those for invasive ER+ breast cancer.ConclusionsOur findings suggest that most risk factors for invasive ER+ breast cancer are also associated with increased risk of ER+ DCIS among African American women.     

Radiation therapy utilization and outcomes for older women with breast cancer: Impact of molecular subtype and tumor grade

BackgroundRadiation therapy (RT) utilization for elderly women with respect to human epidermal growth factor receptor 2 (HER2) receptor status has not been evaluated. Our purpose was to determine differences in RT utilization and breast cancer specific survival (BCSS) for elderly breast cancer patients with distinct molecular biomarkers.MethodsThe Surveillance, Epidemiology, and End Results database was queried for women ≥70 years of age diagnosed with T1N0M0 breast cancer between 2010 and 2013 receiving breast conservation. Chi-squared analysis was performed to determine the difference in RT utilization between groups. Multivariable logistic regression analysis was performed to determine predictors for RT use. Kaplan-Meier curves were created and the log-rank test done to compare differences in breast cancer specific survival (BCSS) between groups.ResultsA total of 12,312 patients met the inclusion criteria. Receipt of RT for patients with distinct tumor biomarkers was as follows: 55.7% for patients with Estrogen Receptor (ER) +/HER2+; 57.1% for patients with ER+/HER2-; 65.6% for patients with ER-/HER2+; and 69.2% for ER-/HER2- patients (p < 0.001). Factors associated with RT use included ER-/HER2- status, 70–74 years of age, and high grade disease, while adjuvant RT was associated with improve BCSS in ER+/HER2- and ER-/HER2- patients.ConclusionsPatients 70–74 years old and those with ER-/HER2- are more likely to receive adjuvant RT. Moreover, adjuvant RT is associated with improvements in BCSS in ER+/HER2- and ER-/HER2- patients. Given possible poor compliance with hormonal therapy, the omission of RT in ER + patients, without consideration of HER2 status, should be undertaken with care.     

Factors influencing local control in patients undergoing breast conservation surgery for ductal carcinoma in situ

BackgroundThe aim of our study was to assess various predictors for local recurrence (LR) in patients undergoing breast conservation surgery (BCS) for ductal carcinoma in situ (DCIS).Materials and methodsAn audit was performed of 582 consecutive patients with DCIS between Jan 1975 to June 2008. In patients undergoing BCS, local guidelines reported a margin of ≥10 mm during the above period. Guideline with regard to margin of excision changes soon after this period.We retrospectively analysed clinical and pathological risk factors for local recurrence in patients undergoing BCS. Statistical analysis was carried out using SPSS version 19, and a cox regression model for multivariate analysis of local recurrence was used.ResultsOverall 239 women had BCS for DCIS during the above period. The actuarial 5-year recurrence rate was 9.6%. The overall LR rate was 17% (40/239. LR was more common in patients ≤50 years: (10/31 patients, 32%) compared to patients > 50 years (30/208, 14%, P = 0.02). Forty three per cent of patients (6/14) with <5 mm margin developed LR which was significantly higher compared to patients with 5–9 mm margin (12%, 3/25) and with ≥10 mm margin (14%, 27/188, P = 0.01). On multivariate analysis age ≤50 years, <5 mm pathological margin were independent prognostic factors for local recurrence.ConclusionOur study shows that younger age (≤50 years) and a margin < 5 mm are poor prognostic factors for LR in patients undergoing breast conservation surgery for DCIS.