Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.     

Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy

BACKGROUND: The current study identified determinants of systemic recurrence and disease-specific survival (DSS) in patients with early-stage breast carcinoma treated with breast-conserving surgery and radiation therapy (breast-conserving therapy, or BCT). METHODS: The study population consisted of 1,043 consecutive women with Stages I or II breast carcinoma who underwent BCT between 1970 and 1994. Clinical and pathologic characteristics evaluated included age, tumor size, tumor grade, estrogen and progesterone receptor status, surgical margins, axillary lymph node involvement, and use of adjuvant therapy. RESULTS: At a median follow-up time of 8.4 years, 127 patients (12%) had developed an ipsilateral breast tumor recurrence (IBTR), and 184 patients (18%) had developed a systemic recurrence. On multivariate logistic regression analysis, tumor size greater than 2 cm, positive lymph nodes, lack of adjuvant tamoxifen therapy, and positive margins (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.034) were predictors of systemic recurrence. When IBTR was added into the model, adjuvant therapy and surgical margins were not independent predictors; however, IBTR was an independent predictor of systemic recurrence (IBTR vs. no IBTR; OR, 6.2; 95% CI, 3.1-12.3; P < 0.001). The 10 year DSS rate after BCT was 87%. On multivariate Cox proportional hazards model analysis, the following factors were independent predictors of poor DSS: tumor size greater than 2 cm (vs. < or = 2 cm; relative risk [RR], 2.3; 95% CI, 1.2-4.3; P = 0.010), negative progesterone receptor status (vs. positive; RR, 2.7; 95% CI, 1.4-5.1; P = 0.003), positive margins (vs. negative; RR, 3.9; 95% CI, 1.4-11.5; P = 0.011), and IBTR (vs. no IBTR; RR, 5.5; 95% CI, 2.8-11.0; P < 0.001). CONCLUSIONS: Positive surgical margins and IBTR are predictors of systemic recurrence and disease-specific survival after BCT. Aggressive local therapy is necessary to ensure adequate surgical margins and to minimize IBTR.     

Ipsilateral breast tumor recurrence (IBTR) after breast-conserving treatment for early breast cancer: risk factors and impact on distant metastases

BACKGROUND: The clinical features of ipsilateral breast tumor recurrence (IBTR) after breast conserving therapy (BCT) for early stage breast cancer were analyzed from long-term follow-up of BCT in Japan. The purpose of this study was to clarify risk factors of IBTR and the impact of IBTR on development of distant metastases in this ethnic group. METHODS: Patients (N = 1901)with unilateral breast cancer < or = 3 cm in diameter who underwent BCT at 18 Japanese major breast cancer treatment institutes from 1986 to 1993 were registered in this study. Survival rates, the incidences of IBTR and distant metastases, and annual rates of IBTR and distant metastases after primary operation were calculated by the Kaplan-Meier method. A Cox proportional hazards model was used to estimate the risks of IBTR and distant metastases. A Cox model was also used to estimate the risks of distant metastases after IBTR in the group of IBTR. RESULTS: At a median follow-up time of 107 months, the 10-year overall and disease-free survival rates were 83.9% and 77.8%, respectively. The 10-year cumulative rates of IBTR were 8.5% in the patients with postoperative irradiation and 17.2% in the patients without irradiation. The 10-year cumulative distant metastasis rate was 10.9%. On multivariate analysis, young age, positive surgical margin, and omission of radiation therapy were significant predictors of IBTR. In addition, IBTR significantly correlated with subsequent distant metastases (hazard ratio, 3.93; 95% confidence interval, 2.676-5.771; P < 0.0001). Among patients who developed IBTR, initial lymph node metastases and short interval to IBTR were significant risk factors for subsequent distant metastasis. CONCLUSIONS: Young age, positive surgical margin, and omission of radiation therapy seemed to be important factors in relation to local control. The authors' results also indicated that IBTR is significantly associated with subsequent distant metastasis. Patients with positive nodal status at primary operation or with short interval from primary operation to IBTR are at especially high risk of distant metastasis. It remains unclear, however, whether IBTR is an indicator or a cause of subsequent distant metastases.     

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.     

Clinical outcome of breast conservation therapy for breast cancer in Hong Kong: prognostic impact of ipsilateral breast tumor recurrence and 2005 St. Gallen risk categories

PURPOSE: The aim of this study was to evaluate the clinical outcome of breast conservation therapy (BCT) for invasive breast cancers in our predominantly Chinese population. METHODS AND MATERIALS: Clinical outcomes of 412 T1-2 invasive breast cancers treated by wide local excision and external radiotherapy from 1994 to 2003 were retrospectively analyzed. Only 7% lesions were first detected by mammograms. Adjuvant tamoxifen and chemotherapy were added in 74% and 45% patients, respectively. RESULTS: The median follow-up was 5.4 years. The 5-year actuarial ipsilateral breast tumor recurrence (IBTR) rate, distant failure-free survival, cause-specific survival, and overall survival were 4%, 92%, 96%, and 98%, respectively. The 5-year distant failure-free survival for the low-risk, intermediate-risk, and high-risk categories (2005 St. Gallen) were 98%, 91%, and 80%, respectively (p = 0.0003). Cosmetic results were good to excellent in more than 90% of the assessable patients. Grade 3 histology (hazard ratio [HR], 4.461; 95% CI, 1.216-16.360; p = 0.024), age (HR, 0.915; 95% CI, 0.846-0.990; p = 0.027), and close/positive final margins (HR, 3.499; 95% CI, 1.141-10.729; p = 0.028) were significant independent risk factors for IBTR. Both St. Gallen risk categories (p = 0.003) and IBTR (HR, 5.885; 95% CI, 2.494-13.889; p < 0.0005) were independent prognostic factors for distant failure-free survival. CONCLUSIONS: Despite the low percentage of mammographically detected lesions, the overall clinical outcome of BCT for invasive breast cancers in the Chinese population is comparable to the Western series. The 2005 St. Gallen risk category is a promising clinical tool, but further validation by large studies is warranted.     

Second invasive breast cancers in patients treated with breast-conserving therapy

ObjectiveSecond breast cancers after breast-conserving therapy (BCT) include ipsilateral breast tumor recurrence (IBTR) and metachronous contralateral breast cancer (CBC). Each IBTR is further classified as true recurrence (TR) or new primary tumor (NP). We aim to compare survival outcomes of TR, NP and CBC, and explore the optimal treatments.Methods168,427 patients with primary breast cancer who underwent BCT between 1990 and 2005 were identified in the SEER database. The risks of IBTR and CBC were estimated by annual hazard rate. The breast cancer-specific survival (BCSS) were assessed using multivariable Cox regression analysis.ResultsWith median follow-up of 13 years after BCT, 5413 patients developed an IBTR and 4050 patients had a CBC. The risk of IBTR peaked between 10 and 15 years after BCT, while the risk of CBC distributed evenly. 45.9% of IBTRs were classified as a TR and 54.1% as an NP. The time interval from primary breast cancer to NP was longer than to TR and CBC (P < 0.001). Patients with TR had a poorer BCSS than NP (P = 0.003) and CBC (P = 0.002). There was no difference in BCSS between mastectomy and repeat BCT for treating TR (P = 0.584) or NP (P = 0.243). The BCSS of CBCs treated with BCT was better than mastectomy (P = 0.010). Chemotherapy didn't improve the survival of patients with TR (P = 0.058). However, TRs with grade III or negative hormone receptors benefited from chemotherapy significantly.ConclusionPatients with TR had a poorer BCSS than NP and CBC. Classifying IBTR may provide clinical significance for treatments.     

The Salzburg concept of intraoperative radiotherapy for breast cancer: results and considerations

Aim of this study is to show that ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery can be reduced by proper surgery and modern radiotherapy techniques. Three hundred and seventy eight women with stage I or II breast cancer had breast conserving surgery and received 51-56.1 Gy of postoperative radiation to the whole breast in 1.7 Gy fractions, but patients received different boost strategies. Group 1 (n = 188) received electron boost radiation of 12 Gy subsequent to the irradiation to the whole breast, group 2 (n = 190) received intraoperative electron boost radiation of 9 Gy directly to the tumor bed, followed by whole breast irradiation. After a median follow up period of 81.0 months in group 1 and a median follow up period of 51.1 months in group 2, 12 IBTRs (6.4%) could be observed in group 1 and no IBTR could be observed in group 2 (0.0%). The 5-year actuarial rates of IBTR were 4.3% (95% CI, 1.9-8.3%) and 0.0% (95% CI, 0.0-1.9%), respectively (p = 0.0018). The 5-year actuarial rates of distant recurrence were 8.6% (95% CI, 4.9-13.5%) and 4.2% (95% CI, 1.8-8.2%), respectively (p = 0.08). The 5 year disease-free survival rates were 90.9% (95% CI, 85.8-94.7%) in group 1 and 95.8% (95% CI, 91.8-98.2%) in group 2 (p = 0.064). Immediate IORT-boost and whole breast irradiation yields excellent local control at 5 years, and was associated with a statistically significant decreased rate of IBTR compared with a similar cohort of patients treated with whole breast irradiation and conventional electron boost.     

Outcome after ipsilateral breast tumor recurrence in patients who receive accelerated partial breast irradiation

BACKGROUND:

The objective of this study was to examine clinical outcomes and patterns of failure in patients with early stage breast cancer who developed an ipsilateral breast tumor recurrence (IBTR) after breast‐conserving therapy (BCT) using accelerated partial breast irradiation (APBI).

METHODS:

In total, 1440 patients (1449 tumors) with early stage breast cancer who underwent BCT were treated with the MammoSite device to deliver APBI (34 Gray [Gy] in 3.4‐Gy fractions). One thousand two hundred fifty‐five patients (87%) had invasive breast cancer (IBC) (median tumor size, 10 mm), and 194 patients (13%) had ductal carcinoma in situ (DCIS) (median tumor size, 8 mm). The median follow‐up was 60 months.

RESULTS:

Fifty patients (3.5%) developed an IBTR for a 5‐year actuarial rate of 3.61% (3.65% for IBC and 3.36% for DCIS). It was determined that 36 recurrences (72%) represented new primary cancers, and 14 recurrences (28%) represented recurrences of the index lesion. Of the 32 recurrences with known histology, 78% were IBC, and 22% were DCIS. After IBTR, 28 of 38 patients (74%) underwent salvage mastectomy, and 9 of 38 patients (26%) had a second attempt at BCT. Adjuvant therapies included tamoxifen in 8 patients (16%) and systemic chemotherapy in 6 patients (12%). The 3‐year rates of disease‐free survival, cause‐specific survival, and overall survival after IBTR were 58.7%, 92.1%, and 80.5%, respectively.

CONCLUSIONS:

With 5 years of follow‐up, APBI produced clinical outcomes and patterns of failure comparable to those achieved with whole breast irradiation. Patients who developed an IBTR after APBI had excellent 3‐year survival outcomes after salvage treatments. Cancer 2012. © 2012 American Cancer Society.     

When can a second conservative approach be considered for ipsilateral breast tumour recurrence?

BACKGROUND: Mastectomy is considered the treatment of choice in patients with ipsilateral breast tumour recurrence (IBTR) after breast-conserving surgery (BCS). PATIENTS AND METHODS: One hundred and sixty-one patients with invasive IBTR who underwent a second conservative approach were retrospectively evaluated in order to describe prognosis, determine predictive factors of outcome and select the subset of patients with the best local control. RESULTS: Fifty-seven patients (35.4%) relapsed after IBTR. Thirty-four patients (21.1%) had further in-breast recurrences and four patients (2.5%) had skin relapses. Five years cumulative incidence of local relapse was 31.4%. Twenty-four patients (17.8%, 5 years cumulative incidence) died during the follow-up. At the multivariate analysis, recurrent tumour size >2 cm was found to affect local-disease-free survival [hazard ratio (HR): 2.8, 95% confidence interval (CI) 1.2-6.2], whereas Ki-67 >or=20% and time to relapse 48 months, eight (12.8%, 5 years cumulative incidence) had further local relapses. CONCLUSIONS: Some patients with IBTR might receive a second BCS, especially when a good local control can be estimated (small recurrent tumour, late relapse), also taking into account patients' preference.     

Primary chemotherapy for operable breast cancer: incidence and prognostic significance of ipsilateral breast tumor recurrence after breast-conserving surgery.

PURPOSE: To determine the incidence and the prognostic value of ipsilateral breast tumor recurrence (IBTR) in patients treated with primary chemotherapy and breast-conserving surgery. PATIENTS AND METHODS: Between January 1985 and December 1994, 257 patients with invasive T1 to T3 breast carcinoma were treated with primary chemotherapy, lumpectomy, and radiation therapy. The median follow-up time was 93 months. To evaluate the role of IBTR in metastase-free survival, a Cox regression multivariate analysis was performed using IBTR as a time-dependent covariate. RESULTS: The IBTR rates were 16% (+/- 2.4%) at 5 years and 21.5% (+/- 3.2%) at 10 years. Multivariate analysis showed that the probability of local control was decreased by the following independent factors: age < or = 40 years, excision margin < or = 2 mm, S-phase fraction more than 4%, and clinical tumor size more than 2 cm at the time of surgery. In patients with excision margins of more than 2 mm, the IBTR rates were 12.7% at 5 years and 17% at 10 years. Nodal status, age < or = 40 years, and negative estrogen receptor status were predictors of distant disease in the Cox multivariate model with fixed covariates. The contribution of IBTR was highly significant (relative risk = 5.34) when added to the model, whereas age < or = 40 years was no longer significant. After IBTR, 31.4% (+/- 7.0%) of patients developed metastases at 2 years and 59.7% (+/- 8.1%) at 5 years. Skin involvement, size at initial surgery, and estrogen receptor status were predictors of metastases after IBTR. CONCLUSION: IBTR is a strong predictor for distant metastases. There are implications for conservative surgery after downstaging of the tumor and therapy at the time of IBTR.     

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.     

Survival after lumpectomy and mastectomy for early stage invasive breast cancer

BACKGROUND:

Randomized clinical trials (RCT) have demonstrated equivalent survival for breast‐conserving therapy with radiation (BCT) and mastectomy for early‐stage breast cancer. A large, population‐based series of women who underwent BCT or mastectomy was studied to observe whether outcomes of RCT were achieved in the general population, and whether survival differed by surgery type when stratified by age and hormone receptor (HR) status.

METHODS:

Information was obtained regarding all women diagnosed in the state of California with stage I or II breast cancer between 1990 and 2004, who were treated with either BCT or mastectomy and followed for vital status through December 2009. Cox proportional hazards modeling was used to compare overall survival (OS) and disease‐specific survival (DSS) between BCT and mastectomy groups. Analyses were stratified by age group (< 50 years and ≥ 50 years) and tumor HR status.

RESULTS:

A total of 112,154 women fulfilled eligibility criteria. Women undergoing BCT had improved OS and DSS compared with women with mastectomy (adjusted hazard ratio for OS entire cohort = 0.81, 95% confidence interval [CI] = 0.80‐0.83). The DSS benefit with BCT compared with mastectomy was greater among women age ≥ 50 with HR‐positive disease (hazard ratio = 0.86, 95% CI = 0.82‐0.91) than among women age < 50 with HR‐negative disease (hazard ratio = 0.88, 95% CI = 0.79‐0.98); however, this trend was seen among all subgroups analyzed.

CONCLUSIONS:

Among patients with early stage breast cancer, BCT was associated with improved DSS. These data provide confidence that BCT remains an effective alternative to mastectomy for early stage disease regardless of age or HR status. Cancer 2013. © 2012 American Cancer Society.     

Breast-conserving therapy and modified radical mastectomy for primary breast carcinoma: a matched comparative study

Background

To compare two types of therapy for primary breast carcinoma, breast-conserving therapy (BCT) and modified radical mastectomy (MRM), in a matched cohort study.

Methods

A series of 1,746 patients with primary breast cancer treated with BCT or MRM in a single Chinese institute between January 2000 and February 2009 were analyzed retrospectively to compare their outcomes with respect to the incidence of local recurrence (LR), distant metastasis, and survival. The patients were matched with regard to age at diagnosis, spreading to axillary lymph nodes, hormone receptor status, the use of neoadjuvant chemotherapy and maximal tumor diameter. The match ratio was 1:1, and each arm included 873 patients.

Results

The median follow-up period was 71 months. The 6-year disease-free survival (DFS) and 6-year distant disease-free survival (DDFS) rates differed significantly between two groups. The 6-year local recurrence-free survival (LRFS) rates were 98.2% [95% confidence interval (CI): 0.973-0.989] in the BCT group and 98.7% (95% CI: 0.980-0.994) in the MRM group (P=0.182), respectively. DFS rates in BCT and MRM groups were 91.3% (95% CI: 0.894-0.932) and 86.3% (95% CI: 0.840-0.886) (P<0.001), respectively, whereas the DDFS rates in BCT and MRM groups were 93.6% (95% CI: 0.922-0.950) and 87.7% (95% CI: 0.854-0.900) (P<0.001), respectively.

Conclusions

BCT in eligible patients is as effective as MRM with respect to local tumor control, DFS and DDFS, and may result in a better outcome than MRM in Chinese primary breast cancer patients.     

Effect of Breast Conservation Therapy vs Mastectomy on Overall Survival and Breast Cancer-Specific Survival Among Men With Stage I-II Breast Cancer: Analysis of SEER, 2000-2018

BackgroundMale breast cancer is a rare malignant tumor, and outcomes of breast conservation therapy (BCT) are currently lacking.MethodThe retrospective, population-based cohort study included 1369 stage I-II (T1–2 N0–1 M0) male breast cancer patients from the SEER database (2000-2018). The patients were grouped in two groups: BCT group and mastectomy group, according to surgical and radiation therapy. Kaplan-Meier method and univariable Cox proportional hazard analysis were used to compare overall survival (OS) and breast cancer-specific survival (BCSS) between two treatment groups. Propensity score matching (PSM) was performed to balance the confounding factors.ResultsOf the 1369 men, 97 (7%) patients received BCT, 1272 (93%) received mastectomy alone. The 5- and 10-year OS rates were 92.3% and 80.7% for BCT group compared with 80.4% and 61.4% for mastectomy group. The 5- and 10-year BCSS rates were 96.5% and 93.9% for patients undergoing BCT, as compared with 93.1% and 84.4% for patients undergoing mastectomy. Compared with mastectomy group, BCT group showed improved OS (hazard ratio [HR], 0.294; 95% CI 0.138-0.623, P = .002) and BCSS (hazard ratio [HR], 0.182; 95% CI 0.040-0.820, P = .027). Of the 791 patients with T1 stage, BCT showed insignificant association with OS (hazard ratio [HR], 0.555; 95% CI 0.207-1.488, P = .242) and BCSS (hazard ratio [HR], 1.217; 95% CI 0.171-8.675, P = .844).ConclusionThe results of this cohort study suggest that BCT is at least equivalent to mastectomy in male breast cancer patients. The underlying mechanism of this association needs further research.     

Factors Affecting Outcome for Young Women with Early Stage Invasive Breast Cancer Treated with Breast-conserving Therapy

Background Young women have worse outcome following breast-conserving therapy (BCT) than do older patients in many studies. We examined how clinical, pathological, and treatment factors affect these results. Methods Between 1993 and 1999, 130 patients age 40 years or younger with stage I or II breast cancer were treated with BCT. The median radiation dose to the tumor bed was 61 Gy; 80% of patients received chemotherapy; and 29% of 72 patients with estrogen-receptor positive tumors received tamoxifen. Median follow-up was 93 months. Results Fifteen patients (12%) developed an ipsilateral breast tumor recurrence (IBTR), with or without other simultaneous failure sites. The Kaplan-Meier 5- and 8-year actuarial rates were 8% and 14%, respectively. The 74 patients with grade 3 tumors had a higher IBTR rate (8-year actuarial rate, 18%) than the 54 patients with grade 1–2 lesions (7%) (P = 0.09). Six patients developed contralateral breast cancers, and 17 developed distant metastases (DM). The 8-year actuarial rates for freedom-from-DM, relapse-free survival, and overall survival were 85%, 72% and 96%, respectively. Conclusion This represents one of the largest series of young women treated with BCT, using an approach similar to current practice. The IBTR rate was substantially lower than in many past studies, but still higher than would be expected for older women. This appeared largely due to the increased rate of IBTR in patients with grade 3 tumors. If this observation is confirmed, further analysis of this subgroup may lead to ways of reducing the risk of IBTR.     

Impact of primary local treatment on the development of distant metastases or death through locoregional recurrence in young breast cancer patients

In this study, we tested the hypothesis whether breast conserving therapy (BCT) compared with mastectomy is associated with a negative outcome in terms of distant metastases or death (DMD) and investigated the relation between locoregional recurrence (LRR) and DMD in young breast cancer (BC) patients. This study included a consecutive series of 536 patients ≤40 years of age at diagnosis with pathological T1N0-3M0 BC, treated between 1989 and 2005. A multistate survival model was used to evaluate the influences of local treatment and LRR on DMD, adjusted for potential prognostic factors. Patients were treated with mastectomy (N = 213) or BCT (N = 323). Median age at diagnosis was 36.3 years, with a median follow-up of 9.0 years. The 10-year actuarial cumulative incidence of DMD was 30.6 % after mastectomy and 26.3 % after BCT (P = 0.04). In total, 81 (15 %) LRRs were observed. After BCT, patients had a threefold higher risk of LRR than after mastectomy (HR 2.9; 95 % CI 1.6–5.3). Patients with LRR had a higher risk of DMD compared with patients without LRR (HR 5.5; 95 % CI 2.1–14.5). However, BCT was not negatively associated with DMD-after-LRR (HR 0.47; 95 % CI 0.2–1.1, BCT vs mastectomy). In conclusion, although LRR significantly affected DMD, the increased risk of LRR after BCT compared with mastectomy did not lead to a worse DMD outcome in BC patients ≤40 years of age.     

Impact of concurrent versus sequential tamoxifen with radiation therapy in early-stage breast cancer patients undergoing breast conservation treatment.

PURPOSE: To assess the impact of sequencing of tamoxifen and radiation therapy (RT) on outcomes in early-stage breast cancer. PATIENTS AND METHODS: This retrospective study evaluates the effect of the sequence of tamoxifen with RT on outcomes in stage I to II breast cancer patients who underwent breast-conservation treatment (BCT) and received adjuvant tamoxifen, with or without adjuvant chemotherapy. Patients were grouped as concurrent (tamoxifen given during RT followed by continued tamoxifen; 174 patients) and sequential (RT followed by tamoxifen; 104 patients). RESULTS: Median follow-up after RT was 8.6 years for both groups. The pathologic T and N stage, race, estrogen and progesterone status, number of positive nodes, and RT were comparable between the two groups (all P >/= .08). More women age 49 years or younger and women who received chemotherapy were in the sequential group than the concurrent group (6% and 25%, respectively; P < .0001). The sequence of tamoxifen therapy did not influence 10-year local recurrence rates (sequential, 7%; concurrent, 3%; P = .52), overall survival (sequential, 86%; concurrent, 81%; P = .64), or relapse-free survival (sequential, 76%; concurrent, 85%; P = .35). When adjusting age and chemotherapy use in the multivariable Cox model, hazard ratios comparing sequential versus concurrent tamoxifen therapy were 1.56 (95% CI, 0.87 to 2.79), 1.23 (95% CI, 0.63 to 2.41), and 1.22 (95% CI, 0.33 to 4.49) for the overall survival, relapse-free survival, and local recurrence, respectively. CONCLUSION: The therapeutic regimens of tamoxifen given concurrently or sequentially with RT both appear to be reasonable options for patients treated with BCT.     

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.     

Improving local control with breast-conserving therapy: a 27-year single-institution experience

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.     

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.