Should Ductal Carcinoma-in-situ (DCIS) Be Removed from the ASTRO Consensus Panel Cautionary Group for Off-protocol Use of Accelerated Partial Breast Irradiation (APBI)? A Pooled Analysis of Outcomes for 300 Patients with DCIS Treated with APBI

Purpose

To analyze outcomes in patients with ductal carcinoma-in-situ (DCIS) treated with accelerated partial breast irradiation (APBI) within a pooled set of patients.

Methods

A total of 300 women with DCIS underwent APBI between April 1993 and November 2010 as part of American Society of Breast Surgeons MammoSite Registry Trial (n = 192) or at William Beaumont Hospital (n = 108). Patients with pure DCIS <3 cm (n = 125) were assigned to the cautionary risk group per American Society of Radiation Oncology consensus panel guidelines for off-protocol use of APBI and analyzed compared to a pooled invasive suitable (n = 653) risk group and pooled invasive suitable/cautionary (n = 1,298) risk group.

Results

The rate of ipsilateral breast tumor recurrence (IBTR) for all 300 DCIS patients was 2.6 % at 5 years with no regional recurrences, while cause-specific survival was 99.5 % and overall survival (OS) was 96.4 %. When comparing the cautionary DCIS group to the invasive suitable/cautionary group, no difference in IBTR was noted (2.6 vs. 3.1 %, P = 0.90) with significant improvements in distant metastases (0 vs. 2.5 %, P = 0.05), disease-free survival (98.5 vs. 94.4 %, P = 0.05), and OS (95.7 vs. 90.8 %, P = 0.03) noted for DCIS patients. When comparing cautionary DCIS patients to invasive suitable patients, no difference in IBTR were noted (2.6 vs. 2.4 %, P = 0.76), while improved OS for DCIS patients was noted (95.7 vs. 90.9 %, P = 0.02).

Conclusions

This analysis of the largest cohort of patients with DCIS treated with APBI supports previously reported excellent outcomes; as a result of small numbers of events, further data are necessary to confirm these findings.     

Twenty-Year Outcomes after Breast-Conserving Surgery and Definitive Radiotherapy for Mammographically Detected Ductal Carcinoma In Situ

Background

Management of mammographically detected ductal carcinoma in situ (DCIS) at a single institution was reviewed to determine long-term clinical outcomes after treatment with breast-conserving therapy (BCT).

Methods

Data from all patient-cases with DCIS who received BCT between 1980 and 1993 were reviewed. Patient demographics and pathologic factors were analyzed for their effect on outcomes, including ipsilateral breast tumor recurrence (IBTR) and survival. BCT included breast-conserving surgery followed by external-beam radiotherapy to the whole breast, with 86?% of patients receiving a lumpectomy cavity boost. The median dose to the whole breast was 50 Gy and 60.4?Gy to the lumpectomy cavity.

Results

A total of 129 cases were evaluated; the median follow-up was 19.3?years. Twenty-one patients developed an ipsilateral breast tumor recurrence (IBTR), 76.2?% of which were invasive (n?=?16). Fourteen recurrences (66?%) were within the same breast quadrant (true recurrence), while an additional 7 cases developed an IBTR elsewhere in the breast. True recurrences were more prevalent in women <45?years of age (20?%/24?% vs. 5.1?%/8?%) at 10 and 20?years (p?=?0.02). The 5-, 10-, 15-, and 20-year actuarial rates of IBTR for this cohort were 8.7, 10.4, 12.1, and 16.3?% (IBTR), while overall survival at 5, 10, and 20 years was 97.6, 96.8, and 96.8?%, respectively.

Conclusions

Mammographically detected DCIS remains a clinically distinct subset of noninvasive breast cancer. With 20?year follow-up, local control and overall survival are excellent after BCT.     

Breast Cancer Subtype and Distant Recurrence after Ipsilateral Breast Tumor Recurrence

Background

There is little information about the impact of breast cancer subtype on prognosis after ipsilateral breast tumor recurrence (IBTR).

Methods

One hundred eighty-five patients were classified according to breast cancer subtype, as approximated by estrogen receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67, of IBTR, and we evaluated whether breast cancer subtype was associated with distant recurrence after IBTR.

Results

There was a significant difference in distant disease-free survival (DDFS) after IBTR according to breast cancer subtype defined by a cutoff of the Ki-67 index of 20 % (p = 0.0074, log-rank test). The 5-year DDFS rates for patients with luminal A, luminal B, triple-negative, and HER2 types were 86.3, 57.1, 56.6, and 65.9 %, respectively. In addition, breast cancer subtype was significantly associated with distant recurrence after IBTR on adjustment for various clinicopathologic factors (p = 0.0027, Cox proportional hazards model).

Conclusions

Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).     

Breast-Conserving Surgery in BRCA1/2 Mutation Carriers: Are We Approaching an Answer?

Background

Approximately 10% of patients with breast cancer who are treated with breast-conserving surgery (BCS) develop an ipsilateral-breast tumor recurrence (IBTR). The optimal local therapy for women with BRCA-associated breast carcinoma remains controversial. We report the outcome of BCS in BRCA mutation carriers followed at a single institution.

Methods

A total of 54 women with BRCA1/2-associated breast cancer treated with BCS and whole breast radiotherapy were matched for age, tumor size, and time of surgery with 162 patients with sporadic breast cancer who had the same treatment between February 1994 and October 2007. Primary end points were cumulative incidence of IBTR and contralateral breast cancer (CBC). Median follow-up was 4 years for both groups.

Results

Median age was 36 and 37 years for mutation carriers and controls, respectively; mean tumor size was 1.8 cm in carriers and 1.9 cm in controls. Ten-year cumulative incidence of IBTR was 27% for mutation carriers and 4% for sporadic controls (hazard ratio 3.9; 95% confidence interval 1.1–13.8; P = 0.03). Ten-year cumulative incidence of CBC was 25% for mutation carriers and 1% for sporadic controls (P = 0.03).

Conclusions

Our data suggest that IBTR risk after BCS in BRCA1/2 mutation carriers is increased compared with patients who have sporadic breast cancer. Likewise, the risk of CBC seems to be increased in this group. These risks and the likelihood of developing new primary tumors should be discussed with carriers interested in breast conservation as well as when choosing risk-reducing strategies.     

Treatment Efficacy with Accelerated Partial Breast Irradiation (APBI): Final Analysis of the American Society of Breast Surgeons MammoSite® Breast Brachytherapy Registry Trial

Background

The purpose of this study was to examine data on treatment efficacy, cosmesis and toxicities for the final analysis of the American Society of Breast Surgeons MammoSite^® breast brachytherapy registry trial.

Methods

A total of 1,449 cases of early-stage breast cancer underwent breast conserving therapy. The single-lumen MammoSite^® device was used to deliver accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1,255 cases (87 %) had invasive breast cancer (IBC) and 194 cases had DCIS. Median follow-up was 63.1 months with 45 % of all patients having follow-up of 6 years or longer.

Results

There were 41 cases (2.8 %) that developed an ipsilateral breast tumor recurrence (IBTR) for a 5-year actuarial rate of 3.8 % (3.7 % for IBC and 4.1 % for DCIS). Tumor size (odds ratio [OR] = 1.1, p = 0.03) and estrogen receptor negativity (OR = 3.0, p = 0.0009) were associated with IBTR, while a trend was noted for positive margins (OR = 2.0, p = 0.06) and cautionary/unsuitable status compared with suitable status (OR = 1.8, p = 0.07). The percentage of patients with excellent/good cosmetic results at 60, 72, and 84 months was 91.3, 90.5, and 90.6 %, respectively. The overall rates of fat necrosis and infections remained low at 2.5 and 9.6 % with few late toxicity events beyond 2 years. The overall symptomatic seroma rate was 13.4 and 0.6 % beyond 2 years.

Conclusions

The final analysis of treatment efficacy, cosmesis, and toxicity from the American Society of Breast Surgeons MammoSite^® breast brachytherapy registry trial confirms previously noted excellent results and compares favorably with other forms of APBI with similar follow-up and to outcomes seen in selected patients treated with whole breast irradiation.     

The Role of Margin Status and Reexcision in Local Recurrence Following Breast Conservation Surgery

Introduction

Breast conservation surgery (BCS) results in survival equal to mastectomy for early-stage breast cancer. Ipsilateral breast tumor recurrence (IBTR) after BCS is thought to be related to margin status. At our institution, reexcision is performed only if tumor is at inked margin or with extensive disease close to multiple margins. The purpose of this study was to determine rates of reexcision and recurrences among BCS patients using this policy.

Methods

We performed an institutional review board-approved retrospective analysis of BCS patients who underwent surgery between January 2001 and June 2005. We identified patients who had a second breast excision within 8 weeks of the first, and those patients with an IBTR. Clinical and pathologic features of patients’ tumors were reviewed.

Results

We identified 543 patients who underwent BCS, 84 patients (15.5 %) underwent reexcision for margin status. The crude IBTR rate was 3.4 %, and the 5-year local recurrence-free survival of the reexcised group was 90.6 % compared with 97.4 % in the non-reexcised group (p = 0.0097). Of the 64 reexcision patients, 6 (9.4 %) had an IBTR versus 12 (2.6 %) of the 459 non-reexcised patients (p = 0.0151).

Discussion

Our reexcision rate is low compared with other reports. This results from a policy that defines “no tumor on ink” as an adequate margin for BCS, and the use of selective irradiation boosts based on margins assessed by our pathologists. Our local recurrence rate compares favorably with those seen in other studies while minimizing the need for additional operations. A higher IBTR rate after reexcision likely reflects tumor biology.     

Perioperative Breast MRI Is Not Associated with Lower Locoregional Recurrence Rates in DCIS Patients Treated With or Without Radiation

Introduction

For women with ductal carcinoma in situ (DCIS) undergoing breast-conserving surgery (BCS), the benefit of magnetic resonance imaging (MRI) remains unknown. Here we examine the relationship of MRI and locoregional recurrence (LRR) and contralateral breast cancer (CBC) for DCIS treated with BCS, with and without radiotherapy (RT).

Methods

A total of 2,321 women underwent BCS for DCIS from 1997 to 2010. All underwent mammography, and 596 (26 %) also underwent perioperative MRI; 904 women (39 %) did not receive RT, and 1,391 (61 %) did. Median follow-up was 59 months, and 548 women were followed for ≥8 years. The relationship between MRI and LRR was examined using multivariable analysis.

Results

There were 184 LRR events; 5- and 8-year LRR rates were 8.5 and 14.6 % (MRI), respectively, and 7.2 and 10.2 % (no-MRI), respectively (p = 0.52). LRR was significantly associated with age, menopausal status, margin status, RT, and endocrine therapy. After controlling for these variables and family history, presentation, number of excisions, and time period of surgery, there remained no trend toward association of MRI and lower LRR [hazard ratio (HR) 1.18, 95 % confidence interval (CI) 0.79–1.78, p = 0.42]. Restriction of analysis to the no-RT subgroup showed no association of MRI with lower LRR rates (HR 1.36, 95 % CI 0.78–2.39, p = 0.28). No difference in 5- or 8-year rates of CBC was seen between the MRI (3.5 and 3.5 %) and no-MRI (3.5 and 5.1 %) groups (p = 0.86).

Conclusions

We observed no association between perioperative MRI and lower LRR or CBC rates in patients with DCIS, with or without RT. In the absence of evidence that MRI improves outcomes, the routine perioperative use of MRI for DCIS should be questioned.     

Effect of MRI on the Management of Ductal Carcinoma In Situ of the Breast

Introduction

The accuracy of breast magnetic resonance imaging (MRI) for detection of ductal carcinoma in situ (DCIS) has prompted recommendations for its routine preoperative use, but its clinical benefit is debated. We reviewed our experience with MRI in DCIS patients to assess the utility of MRI for surgical planning.

Methods

DCIS patients (2008–2010) were identified through a prospectively maintained database and grouped into MRI and no-MRI groups. The rates of additional biopsies, altered surgical management, and reoperation were compared. Additionally, DCIS size ascertained by mammography, MRI, and final pathology was compared.

Results:

Of 352 DCIS patients, 217 received MRI and 135 did not. The type of initial operation and number of reoperations were similar between the two groups, but successful breast conservation was more frequent in the no-MRI group (p = 0.06). The additional biopsy rate was 38 % in the MRI group versus 7 % in the no-MRI group; ≥2 additional biopsies were performed in 18 % of the MRI group and 2 % of the no-MRI group (p < 0.0001). These yielded a cancer diagnosis in 26 % of MRI and 33 % of no-MRI patients (p = 0.73). MRI was not superior to mammogram in detecting size of DCIS lesions preoperatively; 52 % of mammograms were accurate (within 1 cm) compared with 41 % of MRIs.

Conclusions

DCIS patients who undergo preoperative breast MRI are far more likely to undergo additional biopsies. Unless these can be demonstrated to lead to improved long-term outcomes, the utility of routine preoperative MRI in DCIS patients remains questionable.     

Blurry Boundaries: Do Epithelial Borderline Lesions of the Breast and Ductal Carcinoma In Situ Have Similar Rates of Subsequent Invasive Cancer?

Background

The histology of epithelial “borderline lesions” of the breast, which have features in between atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS), is well described, but the clinical behavior is not. This study reports subsequent ipsilateral breast events (IBE) in patients with borderline lesions compared with those with DCIS.

Methods

Patients undergoing breast-conserving surgery for borderline lesions or DCIS from 1997 to 2010 were identified from a prospective database. IBE was defined as the diagnosis of subsequent ipsilateral DCIS or invasive ductal carcinoma.

Results

A total of 143 borderline-lesion patients and 2,328 DCIS patients were identified. Median follow-up was 2.9 and 4.4 years, respectively. 7 borderline-lesion and 172 DCIS patients experienced an IBE. 5 year IBE rates were 7.7 % for borderline lesions and 7.2 % for DCIS (p = .80). 5 year invasive IBE rates were 6.5 and 2.8 %, respectively (p = .25). Similarly, when analyses were restricted to patients who did not receive radiotherapy, or endocrine therapy, or both, borderline-lesion and DCIS patients did not demonstrate statistically significant differences in rates of IBE or invasive IBE.

Conclusions

When compared with DCIS, borderline lesions do not demonstrate lower rates of IBE or invasive IBE. Despite “borderline” histology, a 5 year IBE rate of 7.7 % and an invasive IBE rate of 6.5 % suggest that the risk of future carcinoma is significant and similar to that of DCIS.     

Tumor Bed Control with Balloon-Based Accelerated Partial Breast Irradiation: Incidence of True Recurrences Versus Elsewhere Failures in the American Society of Breast Surgery MammoSite? Registry Trial

Background

Randomized trials demonstrate that lumpectomy plus whole-breast irradiation (WBI) yields survival equivalent to mastectomy. Studies that use WBI, however, typically report higher tumor bed recurrence rates than elsewhere failures (EF) (historically considered new primary lesions). The rate of true recurrence (TR) versus EF was queried for a large patient cohort treated with accelerated partial breast irradiation (APBI).

Methods

A total of 1,449 cases of early-stage breast cancer were treated on the American Society of Breast Surgeons MammoSite^? Registry Trial with lumpectomy plus balloon-based APBI (34?Gy, 10 BID fractions). A total of 1,255 cases (87?%) had invasive breast cancer, and 194 patients (13?%) had ductal carcinoma in situ. Rates of TR versus EF were calculated and compared to historical WBI controls.

Results

Median follow-up was 60 (range 0?C109) months. Fifty patients (3.5?%) developed an ipsilateral breast tumor recurrence (IBTR). The 5-year actuarial rate of IBTR was 3.6?% (invasive breast cancer 3.6?%, ductal carcinoma in situ 3.4?%). Fourteen IBTR (1.1?%) were TR, while 36 (2.6?%) were EF. Estrogen receptor?Cnegative status was associated with IBTR for invasive malignancies as well as for EF only (p?p?=?0.067) and extensive intraductal component (p?=?0.087). No pathologic factors were explicitly associated with TR.

Conclusions

IBTR after balloon-based APBI is low and similar to rates reported for WBI. In this data set, APBI had fewer tumor bed recurrences (presumably initial cancer recurrences) than EF (presumably new primary lesions). This suggests that balloon-based APBI has a tumor bed control rate that is at least equal to (and potentially higher than) WBI.     

The Target for Statins,HMG-CoA Reductase,Is Expressed in Ductal Carcinoma-In Situ and May Predict Patient Response to Radiotherapy

Background

Patients with ductal carcinoma-in-situ (DCIS) are currently not prescribed adjuvant systemic treatment after surgery and radiotherapy. Prediction of DCIS patients who would benefit from radiotherapy is warranted. Statins have been suggested to exert radio-sensitizing effects. The target for cholesterol-lowering statins is HMG-CoA reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway. The aim of this study was to examine HMGCR expression in DCIS and study its treatment predictive value.

Methods

A population-based cohort including 458 women diagnosed with primary DCIS between 1986 and 2004 were followed until November 2011 to study long-term survival. Tumor tissue microarrays were constructed, and immunohistochemical analyses were performed to detect cytoplasmic protein expression of HMGCR. The association between DCIS HMGCR expression and invasive breast cancer recurrence-free survival (RFS_inv) and overall survival (OS) was analyzed by Kaplan–Meier curves, log rank test, and Cox proportional hazard analysis.

Results

HMGCR was strongly expressed in 24 % of the assessed DCIS samples, moderately expressed in 46 %, and weakly expressed in 23 %; no expression was detected in 7 % of the samples. During the follow-up time (median 13.8 years), 61 patients were diagnosed with an invasive breast cancer recurrence, and 80 patients died. A crude analysis showed no survival benefit from radiotherapy. However, patients with strong HMGCR expression showed an improved RFS_inv (log rank, p = 0.03) and OS (log rank, p = 0.04) after radiotherapy. No statistically significant interaction was observed for HMGCR and radiotherapy (RFS_inv p = 0.69 and OS p = 0.29).

Conclusions

This study demonstrates HMGCR expression in DCIS and suggests HMGCR as a predictive marker of response to postoperative radiotherapy in DCIS, although the test for interaction was nonsignificant. Future DCIS studies addressing the potential of statin treatment targeting HMGCR are warranted.     

Impact of Breast Reconstruction on the Decision to Undergo Contralateral Prophylactic Mastectomy

Background

In the last decade, there has been increasing use of contralateral prophylactic mastectomy (CPM) in patients with unilateral breast cancer and ductal carcinoma-in-situ (DCIS) undergoing mastectomy. Although many factors have been proposed to explain this trend, the impact of breast reconstruction on CPM has not been studied.

Methods

A retrospective review of patients with unilateral invasive breast cancer or DCIS from Surveillance, Epidemiology, and End Results registry data (2004–2008) was conducted. Characteristics of patients undergoing CPM and reconstruction were evaluated.

Results

A total of 102,674 patients diagnosed with DCIS or stage I to III infiltrating breast cancer underwent mastectomy for their primary lesion. Of these, 16,197 patients (16 %) underwent a CPM. A significantly higher proportion of women undergoing CPM had reconstruction performed (46 %) than those patients not undergoing CPM (15 %) (p < 0.001). Of the 20,760 patients (20 %) who underwent reconstruction, 7410 (36 %) had implant reconstruction, 7705 (37 %) tissue reconstruction, and 1941 (9 %) combined tissue/implant reconstruction; there were no data for 3,702 (18 %). There was an increasing trend of patients undergoing reconstruction from 2004 (n = 3390, 16.3 %) to 2008 (n = 5406, 26 %) (p < 0.001). On multivariable analysis, significant variables predicting CPM included age <45 years, stage I disease (odds ratio [OR] 1.44, 95 % confidence interval [CI] 1.35–1.54), lobular histology (OR 1.15, 95 % CI 1.11–1.20), and undergoing breast reconstruction (OR 3.58, 95 % CI 3.41–3.75).

Conclusions

Besides age, undergoing reconstructive surgery is the factor most strongly associated with CPM. This suggests that apart from risk reduction, the availability of and/or patient willingness to undergo breast reconstruction may influence the decision to undergo CPM.     

Factors Influencing Surgical and Adjuvant Therapy in Stage I Breast Cancer: A SEER 18 Database Analysis

Background

Randomized trials have shown no survival difference for patients with stage I breast cancer treated with mastectomy versus breast-conserving surgery (BCS) with radiotherapy (RT). RT is recommended after BCS in order to decrease local recurrence and mortality. We sought to evaluate the treatment trends in patients with stage I breast cancer.

Methods

We used the Surveillance, Epidemiology, and End Results (SEER) database to identify 194,860 women with stage I breast cancer diagnosed from 1988 to 2007. We evaluated factors that were associated surgical treatment and the utilization of RT after BCS.

Results

There was a progressive decline in the proportion of patients with stage I breast cancer who were treated with mastectomy from 1998 to 2007. Significant predictors for being treated with mastectomy included single/divorced women (p = 0.007), white race (p < 0.001), estrogen receptor negativity (p < 0.001), earlier year of diagnosis (p < 0.001), smaller tumor size (p < 0.001), and region (p < 0.001). Twenty percent of the BCS cohort did not receive RT, and this proportion did not change over time. Significant predictors for not receiving RT included small tumor size (p < 0.001), African American race (p < 0.001), increasing age (p < 0.001), single/divorced women (p < 0.001), estrogen receptor negativity (p < 0.001), and region (p < 0.001). The survival for patients treated with BCS and RT was significantly higher than for those who did not receive RT (p < 0.001).

Conclusions

The use of BCS for the treatment of stage I breast cancer increased over time. A constant proportion of patients did not receive RT after BCS. Omission of RT in BCS is associated with an increase in mortality.     

Meta-Analysis to Determine if Surgical Resection of the Primary Tumour in the Setting of Stage IV Breast Cancer Impacts on Survival

Introduction

The role of primary tumor excision in patients with stage IV breast cancer is unclear. Therefore, a meta-analysis of relevant studies was performed to determine whether surgical excision of the primary tumor enhances oncological outcome in the setting of stage IV breast cancer.

Methods

A comprehensive search for relevant published trials that evaluated outcomes following excision of the primary tumor in stage IV breast cancer was performed using MEDLINE and available data were cross-referenced. Data were extracted following review of appropriate studies by authors. The primary outcome was overall survival following surgical removal of the primary tumor.

Results

Data from ten studies included 28,693 patients with stage IV disease of whom 52.8 % underwent excision of the primary carcinoma. Surgical excision of the primary tumor in the setting of stage IV breast cancer was associated with a superior survival at 3 years (40 % (surgery) versus 22 % (no surgery) (odds ratio 2.32, 95 % confidence interval 2.08–2.6, p < 0.01). Subgroup analyses for selection of patients for surgery or not, favored smaller primary tumors, less competing medical comorbidities and lower metastatic burden (p < 0.01). There was no statistical difference between the two groups regarding location of metastatic disease, grade of tumor, or receptor status.

Conclusions

Patients with stage IV disease undergoing surgical excision of the primary tumor achieve a superior survival rate then their nonsurgical counterparts. In the absence of robust evidence, this meta-analysis provides evidence base for primary resection in the setting of stage IV breast cancer for appropriately selected patients.     

Cost Comparison of Radiation Treatment Options After Lumpectomy for Breast Cancer

Background

Radiation therapy (RT) after lumpectomy for breast cancer can be delivered with several different regimens. We evaluated a cost-minimization strategy to select among RT options.

Methods

An institutional review board (IRB)-approved retrospective review identified a sample of 100 women who underwent lumpectomy for invasive or in situ breast cancer during 2009. Post lumpectomy RT options included: no radiation in women ≥70 years [T1N0, estrogen receptor (ER)+] per Cancer and Leukemia Group B (CALGB) 9343 (no-RT), accelerated external-beam partial-breast irradiation (APBI), and Canadian fractionation (C-RT), as alternatives to standard whole-breast radiation therapy (WBRT). Eligibility for RT regimens was based on published criteria. RT costs were estimated using the 2011 US Medicare Physician Fee Schedule and average Current Procedural Terminology (CPT) codes billed per regimen at our institution. Costs were modeled in a 1,000-patient theoretical cohort.

Results

Median patient age was 56.5 years (range 32–93 years). Tumor histology included invasive ductal cancer (78 %), ductal carcinoma in situ (DCIS) (15 %), invasive lobular cancer (6 %), and mixed histology (1 %). Median tumor size was 1 cm (range 0.2–5 cm). Estimated per-patient cost of radiation was US$5,341.81 for APBI, US$9,121.98 for C-RT, and US$13,358.37 for WBRT. When patients received the least expensive radiation regimen for which they were eligible, 14 % received no-RT, 44 % received APBI, 7 % received C-RT, and 35 % defaulted to WBRT. Using a cost-minimization strategy, estimated RT costs were US$7.67 million, versus US$13.36 million had all patients received WBRT, representing cost savings of US$5.69 million per 1,000 patients treated.

Conclusions

A cost-minimization strategy results in a 43 % reduction in estimated radiation costs among women undergoing breast conservation.     

Surgical Outcomes of Primary Versus Post-Neoadjuvant Chemotherapy Breast Conservation Surgery: A Comparative Study from a Developing Country

Introduction

In India and other developing countries, breast conservation surgery (BCS) rates in breast cancer patients are low due to advanced disease at presentation and misconceptions about BCS outcomes. Many patients presenting with large or locally advanced breast cancers (LABC) can be offered post-neoadjuvant chemotherapy (NACT) BCS, safety of which is not as well established as that of primary BCS. This retrospective study compared pathological and surgical outcome parameters in patients undergoing primary and post-NACT BCS.

Methods

All non-metastatic breast cancer patients undergoing BCS during 2011–2015 with 1-year follow-up were included. Outcome parameters in form of margin infiltration, ipsilateral breast tumor recurrence (IBTR) rates and IBTR-free survival were compared between primary and post-NACT BCS patients groups.

Results

One hundred and twenty-nine patients underwent BCS; 95 underwent primary and 34 post-NACT BCS. Patients in both groups underwent similar multimodality treatment as per institutional protocols. Post-NACT patients more frequently required oncoplastic volume displacement or replacement surgery (p = 0.002). Re-excision of infiltrated margins was needed more frequently in primary BCS compared with post-NACT BCS group (14.4 vs. 8.8%; p = 0.40). IBTR (Mean follow-up = 30.7 months) was seen in 8.8% post-NACT patients compared with 2.1% primary BCS (p = 0.114). IBTR-free survival did not differ significantly between the groups in stage-wise comparison.

Conclusion

Post-NACT BCS is safe even in large tumors and LABC, though many require oncoplastic procedures for satisfactory cosmesis. In a developing country where many patients present with large breast cancers or LABC, the benefits of BCS can be offered to a majority with the help of NACT, without compromising the chances of cure.

     

Incidence and Consequence of Close Margins in Patients with Ductal Carcinoma-In Situ Treated with Mastectomy: Is Further Therapy Warranted?

Background

The impact of close margins in patients with ductal carcinoma-in situ (DCIS) treated with mastectomy is unclear; however, this finding may lead to a recommendation for postmastectomy radiotherapy (PMRT). We sought to determine the incidence and consequences of close margins in patients with DCIS treated with mastectomy.

Methods

The records of 810 patients with DCIS treated with mastectomy from 1996 through 2009 were reviewed. Clinical and pathologic factors were analyzed with respect to final margin status. Median follow-up was 6.3 years.

Results

Overall, 94 patients (11.7 %) had close margins (positive, n = 5; negative but ≤1 mm, n = 54; 1.1–2.9 mm, n = 35). Independent risk factors for close margins included multicentricity, pathologic lesion size ≥1.5 cm, and necrosis, but not age, use of skin-sparing mastectomy, or immediate reconstruction (p > 0.05). Seven patients received PMRT, and none had a locoregional recurrence (LRR). Among the remaining 803 patients, the 10-year LRR rate was 1 % (5.0 % for margins ≤1 mm, 3.6 % for margins 1.1–2.9 mm, and 0.7 % for margins ≥3 mm [p < 0.001]). The 10-year rate of contralateral breast cancer was 6.4 %. On multivariate analysis, close margins was the only independent predictor of LRR (p = 0.005).

Conclusions

Close margins occur in a minority of patients undergoing mastectomy for DCIS and is the only independent risk factor for LRR. As the LRR rate in patients with close margins is low and less than the rate of contralateral breast cancer, PMRT is not warranted except for patients with multiple close/positive margins that cannot be surgically excised.     

Predictors of Treatment with Mastectomy, Use of Sentinel Lymph Node Biopsy and Upstaging to Invasive Cancer in Patients Diagnosed with Breast Ductal Carcinoma In situ (DCIS) on Core Biopsy

Background

There are few established indications for sentinel lymph node biopsy (SLNB) in breast ductal carcinoma in situ (DCIS). This study examines factors contributing to the high rate of SLNB in DCIS in Alberta, Canada.

Methods

Patients who underwent definitive surgery from January 2009 to July 2011 for DCIS diagnosed on preoperative core-needle biopsy were identified using a provincial synoptic operative report database (WebSMR). The relationship between baseline patient and tumor characteristics and treatment with total mastectomy (TM), use of SLNB, and upstaging were examined.

Results

There were 394 patients identified in the study cohort. Mean age was 57 years, and average preoperative tumor size was 3 cm. Overall, 148 patients (37.6 %) underwent TM; predictors were preoperative tumor size [odds ratio (OR), 1.92 per 1-cm increase in size; 95 % CI 1.65–2.24] and surgeon. Upstaging to invasive cancer at surgery occurred in 23 %, predicted only by preoperative tumor size (OR 1.14 per 1 cm; 95 % CI 1.03–1.27). SLNB was performed in 306 patients overall (77 %) and 140 of those treated with BCS (61 %). Predictors of SLNB were larger preoperative tumor size (OR 1.55 per 1 cm; 95 % CI 1.18–2.04) and the surgeon. In patients treated with BCS, 3 patients who were upstaged had positive SLNs (>0.2 mm), and no patients with DCIS had a positive SLN.

Conclusions

SLNB use is high in patients undergoing BCS for DCIS. Tumor size and the operating surgeon predicted SLNB use. Despite a 23 % upstaging rate, the rate of clinically significant positive SLNs in patients treated with BCS is low, supporting omission of upfront SLNB.     

Metaplastic Breast Cancer: To Radiate or Not to Radiate?

Background

The role of radiation therapy (RT) is unclear for metaplastic breast cancer (MBC). We hypothesized that RT would improve overall survival (OS) and disease-specific survival (DSS).

Materials and Methods

We used the Surveillance, Epidemiology, and End Results (SEER) database to identify MBC patients diagnosed from1988 to 2006. Univariate analyses of patient, tumor, and treatment-specific factors on OS and DSS were performed using the Kaplan–Meier method and differences among survival curves assessed via log rank. Variables assessed included patient age, race/ethnicity, histologic subtype, tumor grade, T stage, N stage, M stage, hormone receptor status, surgery type, and use of RT. Cox proportional hazards models used all univariate covariates. Risks of mortality were reported as hazard ratios (HR) with 95% confidence intervals (95% CI); significance was set at P ≤ 0.05.

Results

Among 1501 patients, RT was given to 580 (38.6%). Ten-year OS and DSS were 53.2, and 68.3%, respectively. In the overall analysis, RT provided an OS (HR 0.64; 95% CI, 0.51–0.82; P < 0.001) and DSS (HR 0.74; CI, 0.56–0.96; P < 0.03) benefit. When patients were stratified according to type of surgery, RT provided an OS but not a DSS benefit to lumpectomy (HR 0.51; CI, 0.32–0.79, P < 0.01) and mastectomy patients (HR 0.67; CI, 0.49–0.90; P < 0.01).

Conclusions

Our findings support the use of RT for patients with MBC following lumpectomy or mastectomy. These retrospective findings should be confirmed in a prospective clinical trial.