Concurrent lobular neoplasia increases the risk of ipsilateral breast cancer recurrence in patients with ductal carcinoma in situ treated with breast‐conserving therapy

BACKGROUND:

Multiple clinicopathologic factors have been analyzed for their association with an increased risk of ipsilateral breast tumor recurrence (IBTR) after women receive breast‐conserving treatment (BCT) for ductal carcinoma in situ (DCIS). The reported incidence of proliferative lesions, such as atypical ductal hyperplasia (ADH), columnar cell changes (CCC), and lobular neoplasia associated with breast cancer, has been as high as 23%; however, the relevance of these lesions on the natural history of DCIS and the risk of IBTR remains unknown.

METHODS:

Two hundred ninety‐four patients with DCIS who received BCT between 1991 and 1995 were identified from the authors' institutional database. Slides were reviewed by a dedicated breast pathologist with particular attention to the presence of lobular neoplasia, ADH, and CCC. The actuarial 5‐, 10‐, and 15‐year IBTR rates were calculated using the Kaplan‐Meier method and were compared using the log‐rank test.

RESULTS:

Concurrent lobular neoplasia was present in 41 of 294 patients (14%), ADH was present in 37 of 294 patients (13%), and CCC was present in 71 of 294 patients (24%). The median follow‐up was 11 years. IBTR occurred in 40 of 227 patients without lobular neoplasia (18%) versus 15 of 41 patients with lobular neoplasia (37%; P=.005; hazard ratio [HR], 2.49). The 5‐, 10‐, and 15‐year cumulative incidence rates of IBTR were twice as high in women who had DCIS and lobular neoplasia compared with women who had DCIS alone (P=.002). Concomitant ADH (HR, 1.53) and CCC (HR, 1.24) were not associated significantly with IBTR (P=.20 and P=.44, respectively).

CONCLUSIONS:

Concurrent lobular neoplasia is associated with a significantly higher risk of IBTR in women with DCIS who received BCT. Women with coexisting DCIS and lobular neoplasia who receive BCT should consider using additional risk‐reducing strategies. Cancer 2009. © 2009 American Cancer Society.     

Ipsilateral breast tumor recurrence (IBTR) in patients with operable breast cancer who undergo breast-conserving treatment after receiving neoadjuvant chemotherapy: Risk factors of IBTR and validation of the MD Anderson Prognostic Index

BACKGROUND:

There is limited information about the risk factors for ipsilateral breast tumor recurrence (IBTR) after patients undergo breast‐conserving surgery plus radiotherapy (breast‐conserving treatment [BCT]) subsequent to neoadjuvant chemotherapy (NAC). The objective of the current study was to analyze these risk factors.

METHODS:

The authors collected data from 375 patients who underwent BCT and received NAC and analyzed the risk of IBTR associated with undergoing BCT after NAC. The usefulness of the MD Anderson Prognostic Index (MDAPI) for IBTR also was validated using the current data set.

RESULTS:

The median follow‐up was 47.8 months, and the 4‐year IBTR‐free survival rate was 95.6%. Multivariate analysis demonstrated that estrogen receptor (ER) status and multifocality of the residual tumor were associated significantly with IBTR‐free survival. In addition, patients who had ER‐positive and human epidermal growth factor 2 (HER2)‐negative tumors did not develop IBTR during the observation period. Although prognostic stratification according to MDAPI was relatively good for the prediction of IBTR in the study patients, the IBTR rate in the high‐risk group was not very high and was lower than that in the intermediate‐risk group. Multivariate analyses demonstrated that IBTR was an independent predictive factor for overall survival.

CONCLUSIONS:

ER status and multifocality of the residual tumor after NAC were independent predictors of IBTR after BCT. The MDAPI was barely adaptable to the study patients in terms of predicting IBTR. Patients with ER‐positive and HER2‐negative tumors had a favorable prognosis, whereas patients who developed IBTR after NAC had significantly worse overall survival. The authors propose a new IBTR prognostic index using the 2 factors that were identified as predictive of IBTR: ER status and multifocality of the residual tumor. Cancer 2012. © 2012 American Cancer Society.     

Outcome After Ipsilateral Breast Tumor Recurrence in Patients With Early-Stage Breast Cancer Treated With Accelerated Partial Breast Irradiation

PurposeLimited outcomes exist in patients who develop an ipsilateral breast tumor recurrence (IBTR) after accelerated partial breast irradiation (APBI). The purpose of this study was to evaluate these outcomes and patterns of failure in our cohort of patients undergoing APBI.Methods and MaterialsA total of 534 patients with early-stage breast cancer were treated with APBI between 1993 and 2010. Clinical, pathologic, and treatment-related variables were analyzed. Clinical outcomes, including further IBTR, regional recurrence, disease-free survival, cause-specific survival, and overall survival were analyzed.ResultsEighteen (3.3%) patients developed an IBTR, for a 5-year actuarial rate of 2.0%; 14 (77.8%) of the recurrences were thought to represent new primary cancers. After IBTR, 13 (72.2%) patients were managed with salvage mastectomy and 4 (22.2%) patients with a second attempt at breast-conserving therapy. Five-year rates of disease-free survival, cause-specific survival, and overall survival after salvage mastectomy for IBTR were 81%, 100%, and 100%, respectively. In the 4 patients treated with a second attempt at breast-conserving therapy, no IBTR, axillary failure, regional recurrence, or distant metastases were noted at 5 years.ConclusionsIBTRs that developed after APBI resulted in excellent clinical outcomes comparable with those observed after whole-breast irradiation.     

Three-year analysis of treatment efficacy, cosmesis, and toxicity by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in patients treated with accelerated partial breast irradiation (APBI)

BACKGROUND: This report presents 3 years of data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite (Cytyc, Bedford, Mass) Breast Brachytherapy Registry Trial. METHODS: A total of 1440 patients (1449 cases) with early stage breast cancer who were undergoing breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial breast irradiation (APBI) (34 Gy in 3.4 Gy fractions). Of these, 1255 (87%) cases had invasive breast cancer (IBC; median size = 10 mm), and 194 (13%) cases had ductal carcinoma in situ (DCIS; median size = 8 mm). Median follow-up was 30.1 months. RESULTS: Twenty-three (1.6%) cases developed an ipsilateral breast tumor recurrence (IBTR) for a 2-year actuarial rate of 1.04% (1.11% for IBC and 0.59% for DCIS). No variables were associated with IBTR. Six (0.4%) patients developed an axillary failure. The percentages of breasts with good to excellent cosmetic results at 12 (n = 980), 24 (n = 752), 36 (n = 403), and 48 months (n = 67 cases) were 95%, 94%, 93%, and 93%, respectively. Breast seromas were reported in 23.9% of cases (30% in open-cavity implants and 19% in closed-cavity implants). Symptomatic seromas occurred in 10.6% of cases, and 1.5% of cases developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 37.5 months, the 3-year actuarial rate of IBTR was 1.79%. CONCLUSIONS: Treatment efficacy, cosmesis, and toxicity 3 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up.     

Ductal carcinoma in situ treated with breast-conserving surgery and accelerated partial breast irradiation: comparison of the Mammosite registry trial with intergroup study E5194

BACKGROUND:

The purpose of this study was to determine the ipsilateral breast tumor recurrence (IBTR) in ductal carcinoma in situ (DCIS) patients treated in the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial who met the criteria for E5194 treated with local excision and adjuvant accelerated partial breast irradiation (APBI).

METHODS:

A total of 194 patients with DCIS were treated between 2002 and 2004 in the Mammosite registry trial; of these, 70 patients met the enrollment criteria for E5194: 1) low to intermediate grade (LIG)—pathological size >0.3 but <2.5 cm and margins ≥3 mm (n = 41) or 2) high grade (HG)—pathological size <1 cm and margins ≥3 mm (n = 29). All patients were treated with lumpectomy followed by adjuvant APBI using MammoSite. Median follow‐up was 52.7 months (range, 0‐88.4). SAS (version 8.2) was used for statistical analysis.

RESULTS:

In the LIG cohort, the 5‐year IBTR was 0%, compared with 6.1% at 5 years in E5194. In the HG cohort, the 5‐year IBTR was 5.3%, compared with 15.3% at 5 years in E5194. The overall 5‐year IBTR was 2%, and there were no cases of elsewhere or regional failures in the entire cohort. The 5‐year contralateral breast event rate was 0% and 5.6% in LIG and HG patients, respectively (compared with 3.5% and 4.2%, respectively, in E5194).

CONCLUSIONS:

This study found that patients who met the criteria of E5194 treated with APBI had extremely low rates of recurrence (0% vs 6.1% in the LIG cohort and 5.3% vs 15.3% in the HG cohort). Cancer 2011. © 2010 American Cancer Society.     

Clinical outcomes using accelerated partial breast irradiation in patients with ductal carcinoma in situ

BackgroundLimited data exist on the use of accelerated partial breast irradiation (APBI) in patients with ductal carcinoma in situ (DCIS). The purpose of this analysis was to evaluate clinical outcomes after APBI in patients with DCIS.Patients and MethodsBetween December 2002 and December 2010, 99 patients with DCIS underwent APBI as part of their breast-conserving therapy (BCT). Partial breast irradiation techniques included interstitial brachytherapy, balloon-based brachytherapy, and 3-dimensional conformal radiotherapy (3D-CRT). Clinical outcomes including local recurrence, regional recurrence, disease-free survival (DFS), cause-specific survival, and overall survival (OS) were analyzed.ResultsMean follow up was 3.0 years, with a mean patient age of 61.8 years. At 5 years, the rates of local recurrence and regional recurrence were 1.4% and 0%, respectively. Overall survival was 94%, whereas cause-specific survival was 100%. No difference was noted in local control for each treatment technique. When comparing rates using the Eastern Cooperative Oncology Group (ECOG) E-5194 trial groupings, the rate of local recurrence in our cohort was 2.0% for patients with grade I/II disease < 2.5 cm and 0% for grade III < 1.0 cm, representing a 50% and 100% decrease, respectively, in local recurrence compared with excision alone.ConclusionsPatients with DCIS treated with APBI had excellent clinical outcomes regardless of the APBI technique used. Until the publication of prospective phase III trials, these data confirm previous reports highlighting the efficacy of APBI in the treatment of noninvasive carcinoma of the breast.     

Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

PURPOSE: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. MATERIALS AND METHODS: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). RESULTS: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy < or = 9 MeV (p = 0.03, HR 1.41), final margins < or = 2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. CONCLUSIONS: After treatment for DCIS, 10-year rates of local control, CSS, and overall survival were similar after mastectomy and BCT. Young age (<45 years), close/positive margins (< or = 2 mm), no breast radiation, and lower electron boost energies (< or = 9 MeV) were associated with IBTR. Local failure and predominant nuclear Grade 3 were found to have a small (4%-12%) but statistically significantly negative impact on the rates of distant metastasis and CSS. These results suggest that optimizing local therapy (surgery and radiation) is crucial to improve local control and CSS in patients treated with DCIS.     

Potential applicability of balloon catheter-based accelerated partial breast irradiation after conservative surgery for breast carcinoma

BACKGROUND: Balloon catheter-based accelerated partial breast irradiation (APBI) is an alternative to whole-breast external-beam irradiation during breast-conserving therapy (BCT) for breast carcinoma, but it is limited by the size of the segmental mastectomy cavity. There are scant data on the average or optimal volume of resection (VR) in BCT. The objective of the current study was to evaluate the percentage of patients who would be eligible for balloon catheter-based APBI based on the selection criteria of the American Society of Breast Surgeons and the surgical VR. METHODS: The authors reviewed the medical records of 443 patients with ductal carcinoma in situ (DCIS) or invasive carcinoma treated with BCT. Patient treatment and pathologic data were analyzed to assess VR and eligibility for APBI. RESULTS: BCT was performed for 178 patients with DCIS and 267 patients with invasive breast carcinoma. The majority of invasive carcinomas (63.3%) were infiltrating ductal carcinomas. The median overall lumpectomy volume was 67.61 cm3, with no significant difference between DCIS and invasive carcinoma (P>0.05). Although the majority (62.9-82.0%) of patients met the individual selection criteria for APBI, only 27.4% of the cohort was found to be eligible for any type of APBI when the selection criteria were considered together. Based on VR, only approximately one-half of the patients initially eligible for APBI would be candidates for immediate balloon catheter-based APBI using the 70 cm3 balloon device (13.3%). However, with the new, larger 125 cm3 balloon device, approximately three-fourths of patients initially eligible for APBI would be eligible for balloon catheter-based APBI at the time of the initial surgical procedure (20.7%). Although not evaluated in the current study, shrinkage of the lumpectomy cavity with time may increase the number of patients eligible based strictly on VR criteria. Patients with a very large VR (> or =125 cm3) were more likely to have invasive carcinoma (P=0.02; hazard ratio [HR], 7.4) and tumors > or =5 cm on final pathology (P<0.01; HR, 22.0). CONCLUSIONS: Approximately one-fifth to one-fourth of patients presenting for BCT may be eligible for balloon catheter-based APBI according to accepted national guidelines and VR. VR must be considered when selecting patients for balloon catheter-based APBI, because a minority of patients will have a lumpectomy cavity that exceeds the size limit of the current balloon device.     

Breast conservation for ductal carcinoma in situ: Results at an Australian institution with evidence to recommend prospective assessment of the utility of a lumpectomy boost

Aim: We reviewed outcomes for ductal carcinoma in situ (DCIS) of the breast at our institution to assess risk factors for ipsilateral breast tumour recurrence (IBTR) after breast conservation (BCT). Methods: Records were reviewed of all patients who presented with biopsy‐confirmed DCIS of the breast prior to 1 January 2004. Variables analyzed included patient age, tumour size, grade, resection margins, comedonecrosis, surgery, tamoxifen, whole breast radiotherapy dose and addition of a boost. We also attempted to validate the University of Southern California/Van Nuys prognostic index (USC/VNPI). Results: One hundred and thirty patients had DCIS: four were excluded from analysis and another 10 had mastectomies. A total of 116 patients had BCT and this group comprised the study population. Median follow‐up was 7.7 years (1.6–12.4) and median age was 58 years. Five‐ and 10‐year overall survivals were 98% (93.5–99.6 95% CI) and 89% (74–95 95% CI). Five‐ and 10‐year breast failure‐free survivals were 96% (90–98 95% CI) and 93% (85–97 95% CI). Young age was the only significant factor associated with IBTR (P = 0.018). Patients with a high USC/VNPI score were also significant for increased IBTR (P = 0.04), but this effect disappeared when age was omitted from the index. There was a trend towards an increased risk of IBTR with a lower whole breast dose of less than 50 Gy (P = 0.18). A boost was not associated with reduced IBTR. The 10‐year IBTR for patients under 55 who received adjuvant radiotherapy to a whole breast dose of <50 Gy but no tamoxifen was 25%. Conclusion: Overall BCT local control and survival outcomes are excellent. There is a suggestion that younger patients should be treated with a whole breast dose equivalent to 50 Gy in 25 daily fractions regardless of a boost. However, this requires confirmation in a randomized phase III trial and therefore the currently active Trans‐Tasman Radiation Oncology Group randomized controlled trial 07.01 should be supported by the breast cancer treating community.     

Five‐year outcome of patients classified using the American Society for Radiation Oncology consensus statement guidelines for the application of accelerated partial breast irradiation

BACKGROUND:

The American Society for Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) was applied to patients who were treated with this technique on the American Society of Breast Surgeons MammoSite Registry Trial to determine potential differences in clinical outcome based on classification group.

METHODS:

Patients were classified based on the CS groups of “suitable,” “cautionary,” and “unsuitable.” Rates of ipsilateral breast tumor recurrence (IBTR), regional lymph node failure, distant metastases, disease‐free survival, cause‐specific survival, and overall survival were assessed.

RESULTS:

Of the 1449 cases who were treated, 1025 patients (71%) could be classified according to the CS groupings, including 419 patients (41%) who fit the “suitable” criteria, 430 patients (42%) who fit the “cautionary” criteria, and 176 patients (17%) who fit the “unsuitable” criteria. At a median follow‐up of 53.5 months, the 5‐year actuarial rates of IBTR for the “suitable,” “cautionary,” and “unsuitable” groups were 2.59%, 5.43%, and 5.28%, respectively (P = .1884). Univariate analysis of factors potentially associated with IBTR indicated that negative estrogen receptor status was the only variable associated with IBTR among patients with invasive breast cancer (odds ratio [OR], 4.01; P = .0003). Larger tumor size was associated with a greater risk of distant metastasis (OR, 3.05; P = .0001). Among patients with ductal carcinoma in situ, only age <50 years and close‐positive margins were associated with IBTR (OR, 1.12 [P = .0079] and OR, 7.81 [P = .0131], respectively).

CONCLUSIONS:

The ASTRO CS groupings did not differentiate a subset of patients with a significantly worse rate of IBTR when they were treated with the MammoSite breast brachytherapy catheter to deliver APBI. Cancer 2010. © 2010 American Cancer Society.     

Preoperative breast magnetic resonance imaging in early breast cancer

BACKGROUND:

Accelerated partial breast irradiation (APBI) of patients with early breast cancer is being investigated on a multi‐institutional protocol National Surgical Adjuvant Breast and Bowel Project (NSABP) B‐39/RTOG 0413. Breast magnetic resonance imaging (MRI) is more sensitive than mammography (MG) and may aid in selection of patients appropriate for PBI.

METHODS:

Patients with newly diagnosed breast cancer or ductal carcinoma in situ (DCIS) routinely undergo contrast‐enhanced, bilateral breast MRI at the Cleveland Clinic. We retrospectively reviewed the medical records of all early‐stage breast cancer patients who had a breast MRI, MG, and surgical pathology data at our institution between June of 2005 and December of 2006. Any suspicious lesions identified on MRI were further evaluated by targeted ultrasound ± biopsy.

RESULTS:

A total of 260 patients met eligibility criteria for NSABP B‐39/RTOG 0413 by MG, physical exam, and surgical pathology. The median age was 57 years. DCIS was present in 63 patients, and invasive breast cancer was found in 197 patients. MRI identified suspicious lesions in 35 ipsilateral breasts (13%) and in 16 contralateral breasts (6%). Mammographically occult, synchronous ipsilateral foci were found by MRI in 11 patients (4.2%), and in the contralateral breast in 4 patients (1.5%). By univariate analysis, lobular histology (infiltrating lobular carcinoma [ILC]), pathologic T2, and American Joint Committee on Cancer stage II were significantly associated with additional ipsilateral disease. Of patients with ILC histology, 18% had ipsilateral secondary cancers or DCIS, compared with 3% in the remainder of histologic subtypes (P = .004). No patient older than 70 years had synchronous cancers or DCIS detected by MRI.

CONCLUSIONS:

Breast MRI identified synchronous mammographically occult foci in 5.8% of early breast cancer patients who would otherwise be candidates for APBI. Cancer 2009. © 2009 American Cancer Society.     

Axillary lymph node failure in patients treated with accelerated partial breast irradiation

BACKGROUND:

Data on the risk of axillary failure (AF) after accelerated partial breast irradiation (APBI) are limited. In this study, the authors determined the rate of AF and regional lymph node failure (RNF) in patients who received various forms of APBI and identified factors that were associated with its occurrence.

METHODS:

In total, 534 patients with early stage breast cancer were treated at William Beaumont Hospital with APBI, including 466 patients (87%) with invasive breast cancer and 68 patients (13%) with ductal carcinoma in situ. Clinical variables (patient age, tumor location), pathologic variables (tumor size, grade, estrogen receptor status, margin status, lymph node status), and treatment‐related variables (receipt of hormone and systemic chemotherapy) were analyzed to determine which factors were associated with AF and RNF. The median length of follow‐up was 63 months (range, 1‐201 months).

RESULTS:

The 5‐year actuarial AF rate was 0.19%. Three patients (0.56%) developed RNF (all patients initially had invasive breast cancer) with a 5‐year actuarial rate of 0.37%. Two of the regional recurrences were in the supraclavicular fossa, and 1 was in the axilla. No variables were associated with AF. However, patient numbers were very small. The median survival after RNF was 0.8 years (range, 0.3‐1.7 years), and 2 of the 3 patients died of disease.

CONCLUSIONS:

The rate of AF and RNF after APBI was low and appeared to be similar to the rate observed with whole‐breast irradiation. No variables were associated with a higher rate of AF after APBI. Cancer 2012;. © 2011 American Cancer Society.     

Twenty-five year results of the national cancer institute randomized breast conservation trial

Breast conservation therapy (BCT) consisting of lumpectomy and postoperative radiation has become an accepted alternative to mastectomy (MRM) for the treatment of early stage breast cancer. We currently report the 25 year outcomes of a single institution, prospective, randomized clinical trial at the National Cancer Institute. 237 women with pathologically confirmed invasive breast tumors 5 cm or less were accrued between 1979 and 1987 and randomized to receive either BCT or MRM. Overall survival was the primary endpoint. Patients with node positive disease were included and treated with doxorubicin and cyclophosphamide. Both arms received axillary dissection. BCT patients had radiation to the whole breast followed by a boost. At a median follow-up of 25.7 years, overall survival was 43.8% for the MRM group and 37.9% for BCT (P = 0.38). Although the cumulative incidence of a disease-free survival event was higher in BCT patients (29.0% MRM vs. 56.4% BCT, P = 0.0017), the additional treatment failures were primarily isolated ipsilateral breast tumor recurrences (IBTR's) requiring salvage mastectomy. 22.3% of BCT patients experienced an IBTR. Distant disease and second cancers were similar in both arms. After 25 years, long term survival between BCT and MRM continues to be similar in patients treated for early stage breast cancer. Patients receiving BCT may be at risk for additional treatment-related morbidity, which may occur as a late event. Further studies are required to delineate patients at higher risk for these events, and prolonged follow up should be encouraged after treatment for all women.     

Ipsilateral breast tumour recurrence in hereditary breast cancer following breast-conserving therapy

The overall rate of an ipsilateral breast tumour recurrence (IBTR) after breast-conserving therapy (BCT) ranges from 1% to 2% per year. Risk factors include young age but data on the impact of BRCA1/2 mutations or a definite positive family history for breast cancer are scarce. We investigated IBTR after BCT in patients with hereditary breast cancer (HBC). Through our family cancer clinic we identified 87 HBC patients, including 26 BRCA1/2 carriers, who underwent BCT between 1980 and 1995 (cases). They were compared to 174 patients with sporadic breast cancer (controls) also treated with BCT, matched for age and year of diagnosis. Median follow up was 6.1 years for the cases and 6.0 years for controls. Patient and tumour characteristics were similar in both groups. An IBTR was observed in 19 (21.8%) hereditary and 21 (12.1%) sporadic patients. In the hereditary patients more recurrences occurred elsewhere in the breast (21% versus 9.5%), suggestive of new primaries. Overall, the actuarial IBTR rate was similar at 2 years, but higher in hereditary as compared to sporadic patients at 5 years (14% versus 7%) and at 10 years (30% versus 16%) (P=0.05). Post-relapse and overall survival was not different between hereditary and sporadic cases. Hereditary breast cancer was therefore associated with a higher frequency of early (2-5 years) and late (>5 years) local recurrences following BCT. These data suggest an indication for long-term follow up in HBC and should be taken into account when additional 'risk-reducing' surgery after primary BCT is eventually considered.     

Differences in survival among women with stage III inflammatory and noninflammatory locally advanced breast cancer appear early: a large population-based study

BACKGROUND:

Significant improvements in the survival of women with breast cancer have been observed and are attributed to a multidisciplinary approach and the introduction of polychemotherapy and endocrine regimens. The objective of this population‐based study was to determine whether women with inflammatory breast cancer (IBC) who received treatment in a modern era had a poorer survival compared those with non‐IBC locally advanced breast cancer (LABC).

METHODS:

The Surveillance, Epidemiology, and End Results program registry was searched to identify women with stage IIIB/C breast cancer diagnosed between 2004 and 2007 who had undergone surgery and radiotherapy. Patients were categorized as either having IBC or non‐IBC LABC according the sixth edition of the American Joint Committee on Cancer (AJCC) criteria. Breast cancer‐specific survival (BCS) was estimated using the Kaplan‐Meier product limit method and compared across groups using the log‐rank statistic. Cox models were then fitted to compare the association between breast cancer type and BCS after adjusting for patient and tumor characteristics.

RESULTS:

A total of 828 (19.2%) women and 3476 (80.8%) women had stage IIIB/C IBC and non‐IBC LABC, respectively. The median follow‐up was 19 months. The 2‐year BCS rate was 90% (95% confidence interval [95% CI], 88%‐91%) for the entire cohort and 84% (95%CI, 80%‐87%) and 91% (95%CI, 90%‐91%) among women with IBC and non‐IBC LABC, respectively. In the multivariable model, patients with IBC were found to have a 43% increased risk of death from breast cancer compared with patients with non‐IBC LABC (hazard ratio, 1.43; 95%CI, 1.10‐1.86 [P = .008]).

CONCLUSIONS:

In the era of multidisciplinary management and anthracycline‐based and taxane‐based polychemotherapy regimens, women with IBC continue to have worse survival outcomes compared with those with non‐IBC LABC. Cancer 2011. © 2010 American Cancer Society.     

Multifocality in ipsilateral breast tumor recurrence - A study in ablative specimens

BackgroundThe incidence and clinical significance of multifocality in ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) are unclear. With growing interest in repeat BCT, this information has become of importance. This study aimed to gain insight in the incidence of multifocality in IBTR, to identify patient- and tumor-related predicting factors and to investigate the prognostic significance of multifocality.MethodsTwo hundred and fifteen patients were included in this analysis. All had an IBTR after BCT and were treated by salvage mastectomy and appropriate adjuvant therapy. Predictive tumor- and patient-related factors for multifocality in IBTR were identified using X2 test and univariate logistic regression analyses. Prognostic outcomes were calculated using Kaplan Meier analysis and compared using the log rank test.ResultsMultifocality was present in 50 (22.9%) of IBTR mastectomy specimens. Axillary positivity in IBTR was significantly associated with multifocality in IBTR. Chest wall re-recurrences occurred more often after multifocal IBTR (14% versus 7% after unifocal IBTR, p = 0.120). Regional re-recurrences did not differ significantly between unifocal and multifocal IBTR (8% vs. 6%, p = 0.773). Distant metastasis after salvage surgery occurred more frequently after multifocal IBTR (15% vs. 24%, p = 0.122). Overall survival was 132 months after unifocal IBTR and 112 months after multifocal IBTR (p = 0.197).ConclusionThe prevalence of multifocality in IBTR is higher than in primary breast cancer. Axillary positivity in IBTR was associated with a multifocal IBTR. Chest wall re-recurrences and distant metastasis were, although not statistically significant, more prevalent after multifocal IBTR.     

Ductal carcinoma in situ of the breast in younger women: A subgroup of patients at high risk

Background

After breast conservative treatment (BCT), young age is a predictive factor for recurrence in patients with Ductal Carcinoma In Situ (DCIS) of the breast. The purpose of this study was to evaluate predictive factors for recurrence and outcomes in these younger women (under 40 years) treated for pure DCIS.

Methods

From 1974 to 2003, 207 cases were collected in 12 French Cancer Centers. Median age was 36.3 years and median follow-up 160 months. Seventy four (35.8%) underwent mastectomy, 67 (32.4%) lumpectomy alone and 66 (31.9%) lumpectomy plus radiotherapy.

Results

37 recurrences occurred (17.8%): 14 (38%) were in situ and 23 (62%) invasive. After BCT, the overall rate of recurrence was 27% (33% in the lumpectomy plus radiotherapy group vs. 21% in the lumpectomy alone group). Comedocarcinoma subtype (p = 0.004), histological size more than 10 mm (p = 0.011), necrosis (p = 0.022) and positive margin status (p = 0.019) were statistically significant predictive factors for recurrence. The actuarial 15-year rates of local recurrence were 29%, 42% and 37% in the lumpectomy alone, lumpectomy and whole breast radiotherapy and lumpectomy + whole breast radiotherapy with additional boost groups respectively. After recurrence, the 10-year overall survival rate was 67.2%.

Conclusion

High recurrence rates (mainly invasive) after BCT in young women with DCIS are confirmed. BCT in this subgroup of patients is possible if clear and large margins are obtained, tumor size is under 11 mm and necrosis- and/or comedocarcinoma-free.     

Early ipsilateral breast tumor recurrences after breast conservation affect survival: an analysis of the National Cancer Institute randomized trial

PURPOSE: To evaluate the effect of an ipsilateral breast tumor recurrence (IBTR) after breast-conservation therapy (BCT) on survival. METHODS AND MATERIALS: One hundred twenty-one women were randomized to BCT. Patients with an IBTR were analyzed to determine survival. Analysis was performed with Kaplan-Meier estimates, log-rank tests, and time-dependent covariate Cox models. RESULTS: At a median follow-up of 18.4 years, 27 patients had an IBTR. The median survival time after IBTR was 13.1 years. The 5-year survival rate was 91.8% (95% confidence interval [CI], 81.5-100%). The 10-year survival rate was 54.3% (95% CI, 35.8-82.6%). According to a Cox model with time-dependent covariates, the hazard ratio or relative risk of dying for those with an IBTR at <5.3 years after BCT relative to patients without an IBTR after BCT is 1.47 (95% CI, 1.02-2.12%; p = 0.04). The hazard ratio for those who relapse after 5.3 years is 0.59 (95% CI, 0.22-1.61%; p = 0.31). Age at randomization, original tumor size, and the presence of positive regional nodes at initial presentation were not found to be associated with decreased survival. CONCLUSIONS: There seems to be a significant association of early IBTR after BCT with decreased survival. Local control should be maximized.     

Ductal carcinoma in situ treated with breast-conserving surgery and radiotherapy: a comparison with ECOG study 5194

BACKGROUND:

Recent data from Eastern Cooperative Oncology Group (ECOG) Study 5194 (E5194) prospectively defined a low‐risk subset of ductal carcinoma in situ (DCIS) patients where radiation therapy was omitted after lumpectomy alone. The purpose of the study was to determine the ipsilateral breast tumor recurrence (IBTR) in DCIS patients who met the criteria of E5194 treated with lumpectomy and adjuvant whole breast radiation therapy (RT).

METHODS:

A total of 263 patients with DCIS were treated between 1980 and 2009 who met the enrollment criteria for E5194: 1) low to intermediate grade (LIG) with size >0.3 cm but <2.5 cm and margins >3 mm (n = 196), or 2) high grade (HG), size <1 cm and margins >3 mm (n = 67). All patients were treated with lumpectomy and whole breast RT with a boost to a median total tumor bed dose of 6400 cGy. Standard statistical analyses were performed with SAS (v. 9.2).

RESULTS:

The average follow‐up time was 6.9 years. The 5‐year and 7‐year IBTR for the LIG cohort in this study was 1.5% and 4.4% compared with 6.1% and 10.5% in E5194, respectively. The 5‐year and 7‐year IBTR for the HG cohort was 2.0% and 2.0% in this study compared with 15.3% and 18% in E5194, respectively.

CONCLUSIONS:

Adjuvant whole breast radiation therapy reduced the rate of local recurrence by more than 70% in patients with DCIS who met the criteria of E5194 (6.1% to 1.5% in the LIG cohort and 15.3% to 2% in the HG cohort). Additional follow‐up is necessary given that 70% of IBTRs occurred after 5 years. Cancer 2011. © 2010 American Cancer Society.     

Repeat lumpectomy for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery: the impact of radiotherapy on second IBTR

Objectives

There are limited data on the outcomes of patients treated with repeat lumpectomy at the time of ipsilateral breast tumor recurrence (IBTR). Especially, the impact of radiotherapy (RT) on a second IBTR is unknown.

Methods

We retrospectively analyzed 143 patients from 8 institutions in Japan who underwent repeat lumpectomy after IBTR. The risk factors of a second IBTR were assessed.

Results

The median follow-up period was 4.8 years. The 5-year second IBTR-free survival rate was 80.7 %. There was a significant difference in the second IBTR-free survival rate according to RT (p = 0.0003, log-rank test). The 5-year second IBTR-free survival rates for patients who received RT after initial surgery, RT after salvage surgery, and no RT were 78.0, 93.5, and 52.7 %, respectively. Multivariate analysis revealed that RT was a significantly independent predictive factor of second IBTR-free survival.

Conclusion

Repeat lumpectomy plus RT is a reasonable option in patients who did not undergo RT at the initial surgery. In contrast, caution is needed when RT is omitted in patients who have undergone repeat lumpectomy.