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.     

Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation

BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.     

Patients with early stage invasive cancer with close or positive margins treated with conservative surgery and radiation have an increased risk of breast recurrence that is delayed by adjuvant systemic therapy

Purpose: The association between a positive resection margin and the risk of ipsilateral breast tumor recurrence (IBTR) after conservative surgery and radiation is controversial. The width of the resection margin that minimizes the risk of IBTR is unknown. While adjuvant systemic therapy may decrease the risk of an IBTR in all patients, its impact on patients with positive or close margins is largely unknown. This study examines the interaction between margin status, margin width, and adjuvant systemic therapy on the 5- and 10-year risk of IBTR after conservative surgery and radiation.

Methods and Materials: A series of 1,262 patients with clinical Stage I or II breast cancer were treated by breast-conserving surgery, axillary node dissection, and radiation between March 1979 and December 1992. The median follow-up was 6.3 years (range 0.1–15.6). The median age was 55 years (range 24–89). Clinical size was T1 in 66% and T2 in 34%. Seventy-three percent of patients were node-negative. Only 5% of patients had tumors that were EIC-positive. Forty-one percent had a single excision, and 59% had a reexcision. The final margins were negative in 77%, positive in 12%, and close (≤ 2 mm) in 11%. The median total dose to the tumor bed was 60 Gy with negative margins, 64 Gy with close margins, and 66 Gy with positive margins. Chemotherapy ± tamoxifen was used in 28%, tamoxifen alone in 20%, and no adjuvant systemic therapy in 52%.

Results: The 5-year cumulative incidence (CI) of IBTR was not significantly different between patients with negative (4%), positive (5%), or close (7%) margins. However, by 10 years, a significant difference in IBTR became apparent (negative 7%, positive 12%, close 14%, p = 0.04). There was no significant difference in IBTR when a close or positive margin was involved by invasive tumor or DCIS. Reexcision diminished the IBTR rate to 7% at 10 years if the final margin was negative; however, the highest risk was observed in patients with persistently positive (13%) or close (21%) (p = 0.02) margins. The median interval to failure was 3.7 years after no adjuvant systemic therapy, 5.0 years after chemotherapy ± tamoxifen, and 6.7 years after tamoxifen alone. This delay to IBTR was observed in patients with close or positive margins, with little impact on the time to failure in patients with negative margins. The 5-year CI of IBTR in patients with close or positive margins was 1% with adjuvant systemic therapy and 13% with no adjuvant therapy. However, by 10 years, the CI of IBTR was similar (18% vs. 14%) due to more late failures in the patients who received adjuvant systemic therapy.

Conclusion: A negative margin (> 2 mm) identifies patients with a very low risk of IBTR (7% at 10 years) after conservative surgery and radiation. Patients with a close margin (≤ 2 mm) are at an equal or greater risk of IBTR as with a positive margin, especially following a reexcision. A margin involved by DCIS or invasive tumor has the same increased risk of IBTR. A reexcision of an initially close or positive margin that results in a negative final margin reduces the risk of IBTR to that of an initially negative margin. A close or positive margin is associated with an increased risk of IBTR even in patients who are EIC-negative or receiving higher boost doses of radiation. The median time to IBTR is delayed; however, the CI is not significantly decreased by adjuvant systemic therapy in patients with close or positive margins—the 5 year results in these patients underestimate their ultimate risk of recurrence.     

In situ breast cancer

Opinion statement The clinical expression of in situ cancer varies widely but is usually occult. Diagnosis can be made by a variety of minimally invasive techniques. Treatment of lobular carcinoma in situ (LCIS) is patient-directed but generally requires only close followup. Mastectomy is the gold standard for ductal carcinoma in situ (DCIS) and is associated with low recurrence rates. Breast conservation therapy (BCT) has become an acceptable alternative. This choice of definitive therapy for DCIS depends largely on the ability to obtain negative margins. Any attempt at BCT should be coupled with the caveat of close postoperative long-term follow-up. Patients diagnosed with LCIS or who have a history of DCIS should be given the options for the use of tamoxifen for the reduction of subsequent development of invasive breast cancer. Risk versus benefits should be clearly defined.     

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.     

Defining the clinical target volume for patients with early-stage breast cancer treated with lumpectomy and accelerated partial breast irradiation: a pathologic analysis

BACKGROUND: This pathologic analysis was conducted to help define the clinical target volume (CTV) for partial breast irradiation (PBI) by analyzing the amount and distance of residual disease found at reexcision after an initial lumpectomy. MATERIALS AND METHODS: The study population consisted of 441 patients derived from a dataset of 607 consecutive cases of Stage I and II breast cancer (reviewed by one pathologist) who underwent reexcision (after lumpectomy) before radiation therapy (RT) as part of their standard breast-conserving therapy (BCT). The assumption in this analysis was that the maximal measured extension distance from the initial excision specimen margin (in the reexcision specimen) represents the minimum distance that needs to receive full-dose RT for PBI to be successful. In 333 of the 441 cases, it was possible to measure this distance. Margins were classified as negative (carcinoma > 1/2 low-power field [LPF] from the margin), near (< 1/2 LPF from the margin), or positive. The amount of carcinoma near the final margin was quantified as the width of invasive carcinoma and number of ductal carcinoma in situ (DCIS) ducts near the margin and divided into three groups: least, intermediate, and greatest amount. RESULTS: Of the 333 cases, 119 (35.7%) had no residual carcinoma in the reexcision specimen, 67 (20.1%) had maximum extension (invasive carcinoma or DCIS) distances of >0<5 mm beyond the initial excision cavity edge, 83 (24.9%) extended 5 to <10 mm, 34 (10.2%) extended 10 to <15 mm, and 30 (9.0%) extended > or =15 mm. In 90% of 134 patients with negative initial lumpectomy margins (per National Surgical Breast and Bowel Project criteria) at lumpectomy, if any residual disease was present (38.2% of cases), it was limited to <10 mm from the edge of the original lumpectomy margin. The initial lumpectomy margin status was then combined with the invasive carcinoma: specimen maximum dimension ratio to determine if these two criteria (when combined) could better identify patients with residual disease limited to <10 mm from the initial margin. Analyzed in this fashion, all 13 of the reexcision specimens (9.7%) with >10 mm of maximum extension by carcinoma beyond the edge of the initial excision specimen cavity could be identified. CONCLUSIONS: A margin of 10 mm around the tumor bed should be adequate in covering disease remaining in the breast after lumpectomy in >90% of patients treated with PBI. However, it is possible to accurately identify all patients with disease extending beyond 10 mm using more restrictive pathologic selection criteria. These results can also be used as a guide for defining the CTV for boost treatment after whole-breast RT and the amount of breast tissue to remove at reexcision.     

乳腺癌保守手术治疗后同侧局部复发危险因素的探讨

目的 探讨临床、病理因素及辅助治疗对乳腺癌保守手术合并放疗后同侧局部复发的影响。方法 应用Kaplan-Meier方法和Cox比例风险模型对126例保乳术合并放疗的早期乳腺癌患者进行回顾性分析。结果 多因素条件下56岁以上乳腺癌患者保乳手术合并放疗后同侧局部复发的风险比为2.17,EIC阳性的风险比为3.46,病灶切缘不净为1.68,无辅助TAM治疗组的风险比为1.52。结论 年龄、EIC及切缘情况对保乳术合并放疗后同侧局部复发有重要的影响,同时辅助TAM治疗可以减少局部复发的风险。     

Use of pathologic factors to assist in establishing adequacy of excision before radiotherapy in patients treated with breast-conserving therapy

BACKGROUND: We reviewed our experience in patients with early-stage breast carcinoma treated with breast-conserving therapy (BCT) to identify pathologic factors useful in defining the adequacy of excision before radiotherapy (RT). METHODS AND MATERIALS: All slides from 607 consecutively treated cases of Stage I-II breast carcinoma were reviewed by one pathologist. Numerous pathologic factors were evaluated for their association with ipsilateral breast failure (IBF). Margin distance was classified as negative, near (<0.50 low-power field), or positive. The amount of carcinoma near the final margin was measured as the width of invasive carcinoma and number of ducts with carcinoma in situ near the margin and divided into three groups: near-least, near-intermediate, and near-greatest amount. The median follow-up was 8.5 years. RESULTS: Patients with negative, near-least, near-intermediate, and near-greatest amount of carcinoma near the margin, and positive final margins had a 12-year IBF rate of 9%, 6%, 18%, 24%, and 30%, respectively. On multivariate analysis, only the amount of carcinoma near the margin was independently associated with IBF (p <0.001). To help explain these observations, 441 initial and reexcision specimens were examined. The amount of carcinoma near the initial margin and the invasive carcinoma/specimen maximal dimension ratio were significantly associated with greater amounts of residual carcinoma in adjacent breast parenchyma. CONCLUSION: The amount of carcinoma near the margin, in addition to margin status, appears to be directly related to an increased risk of IBF in patients treated with BCT. Pathologic factors that incorporate the amount of excised breast parenchyma and amount of carcinoma near the margin may be useful to clinicians in deciding whether a patient has undergone adequate excision for BCT.     

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.     

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.     

Role of resection margins in patients treated with breast conservation surgery

BACKGROUND: After breast conservation therapy (BCT), margin status is routinely evaluated to select patients who need reexcision. The aim of this study was to investigate how margin status and other clinicopathologic factors correlate with the presence of residual tumor at reexcision. METHODS: A series of 431 breast cancer patients who underwent BCT followed by reexcision were considered because they had positive or close (< or =3 mm) margins. At univariate and multivariate analysis the frequency of residual tumor in the reexcision specimens was associated with the status and width of resection margins and with a series of other clinicopathologic factors. RESULTS: Of the 382 evaluable patients, 253 had positive and 129 close margins. Residual tumor was found at reexcision in 51.8% positive-margin patients and 34.1% close-margin patients (P = .001). In the latter group tumor-margin distance (range, 0.08 to 3 mm) was not associated with the incidence of residual tumor (P = .134). On univariate analysis age < or =45 years (P = .006), intraductal histotype (P = .005), size > 2 cm (P = .010), positive axillary nodes (P = .031), and timing of reexcision (P = .044) were significantly associated with a higher frequency of residual tumor. All these factors, except tumor size, maintained a significant predictive value on multivariate analysis. CONCLUSIONS: In the presence of positive margins, relevant residual disease cannot be ruled out and further surgery is indicated. Close margins do not mandate reexcision because they may indicate either that the tumor has been radically excised or the presence of residual foci of a multifocal tumor, which are usually effectively treated by radiotherapy.     

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.     

Indications and limits of breast conserving treatment

In Japan, 41% of surgeries for breast cancer were breast conserving treatment (BCT) in 2000. The indications for BCT in the guidelines of the Japanese Breast Cancer Society (1999) are as follows: (1) tumor size is 3 cm or less, (2) image diagnosis indicates no sign of extensive intraductal spread, (3) cases with multiple tumor are excluded, (4) radiation therapy is possible, (5) the patient wants to receive BCT. The pathological negative margin is favorable in BCT; however, we estimate based on our study that only about 30% of all breast cancers can be completely resected by partial mastectomy. To extend the indications for BCT, the roles of postoperative radiotherapy, endocrine therapy and preoperative chemotherapy will be important. Patients with ipsilateral breast tumor recurrence (IBTR) have increased risk of distant metastases, and the presence of IBTR is an important predictive factor for distant metastases. When we discuss the indications and limits of BCT, we have to take the rate of IBTR into careful consideration.     

Changes in temporal patterns of local failure after breast-conserving therapy and their prognostic implications

PURPOSE: The purpose of this analysis was to evaluate patterns and rates of ipsilateral breast tumor recurrence (IBTR) over time based on the type of failure (true recurrence/marginal miss [TR/MM] vs. elsewhere [E]) and to compare these to rates of contralateral failure in women with Stages I/II breast cancer treated with conservative surgery (CS) and radiation therapy (RT). METHODS AND MATERIALS: Between 1980 and 1997, 1448 patients with Stages I/II invasive breast carcinoma were treated with CS and RT to a median total dose of >60 Gy. IBTRs were analyzed in terms of their location as follows: TR/MM, referring to those occurring in the same quadrant, and E, referring to the development of a malignancy remote from the index lesion. Outcomes were characterized in terms of their temporal recurrence patterns and correlated with rates of contralateral breast failure (CL). The median follow-up was 8.5 years. RESULTS: A total of 79 ipsilateral and 98 contralateral failures were observed during the follow-up period corresponding to 5-, 10-, and 15-year actuarial rates of 2%, 7%, and 10% and 4%, 9%, and 12% respectively. Fifty-nine ipsilateral failures (74.7%) were designated as TR/MM and 20 (25.3%) as E. The corresponding 5-, 10-, and 15-year actuarial rates of TR/MM and E failures were 2%, 5%, and 8% and 0.1%, 2%, and 3%, respectively. The median times to total ipsilateral, TR/MM, E, and contralateral failure were 6.5, 5.7, 7.4, and 5.2 years, respectively. Between 0 and 5 years of follow-up, E failures represented 7% of the total ipsilateral failures observed. From 5-10 and 10-15 years, E failures represented 39% and 27% of the total, respectively (p = 0.01). Contralateral failure was significantly more likely to occur in the first 5 years of follow-up than IBTR, accounting for 50 (63.3%) of the 79 failures in that interval (p = 0.02). No significant differences in survival rates were detected between any of the various failure types. On multivariate analysis, only reduced time to tumor recurrence was found to be adversely associated with overall survival. CONCLUSIONS: The rates and patterns of IBTR vary with time and, after 5 years, approach the rates of development of a contralateral breast cancer. E failures are, overall, less frequent than TR/MM but contribute increasingly to the IBTR rate after 5 years. Time to tumor recurrence is the most reliable predictor of prognosis after IBTR.     

Factors predisposing to cavity margin positivity following conservation surgery for breast cancer

AIMS: Incomplete excision leads to local recurrence following breast conservation therapy (BCT). The aim of this study was to examine factors associated with cavity margin (CM) positivity and return to theatre rates. METHODS: Breast conservation surgery with entire CM excision was the initial procedure in 301 patients with 303 breast cancers. Of these, 258 patients were treated successfully with breast conservation surgery and 43 patients subsequently required a mastectomy for persistent involved margins. The mean and median follow-up was 38 and 42 (range 6-78) months, respectively. RESULTS: Positive CMs were found in 73 out of 303 tumours. Large tumour size (p<0.001) and tumour type (invasive lobular cancer and ductal carcinoma in-situ) (p=0.043) were significant predictors of CM positivity both by univariate and multivariate analysis. As a result of CM status in relation to initial margin (IM) status, 60 cancers treated that were IM positive but CM negative avoided return for further excision at a second operative procedure. CONCLUSION: Complete CM excision should avoid the need for further re-excision surgery in most patients where initial specimen margin was positive.     

Factors associated with local recurrence of mammographically detected ductal carcinoma in situ in patients given breast-conserving therapy

BACKGROUND: The authors reviewed their institution's experience treating patients with mammographically detected ductal carcinoma in situ (DCIS) of the breast with breast-conserving therapy (BCT) to determine 10-year rates of local control and survival and to identify factors associated with local recurrence. METHODS: From January 1980 to December 1993, 132 breasts in 130 patients were treated with BCT for mammographically detected DCIS at William Beaumont Hospital, Royal Oak, Michigan. All patients underwent an excisional biopsy, and 64% were reexcised. All patients received postoperative whole-breast irradiation to a median dose of 45.0 Gray (Gy) (range: 43.1-56.0 Gy). One hundred twenty-four cases (94%) received a boost to the tumor bed for a median total dose of 60.4 Gy (range: 45.0-71.8 Gy). All cases underwent complete pathologic review by one pathologist. The median follow-up was 7.0 years. RESULTS: Of the entire study group, 13 patients developed recurrence within the ipsilateral breast, for 5- and 10-year actuarial rates of 8.9% and 10.3%, respectively. Nine of the 13 recurrences (69%) occurred within or immediately adjacent to the lumpectomy cavity and were designated as true recurrences or marginal misses (TR/MM). Four patients (31%) had recurrence elsewhere in the breast. Ten of the 13 recurrences (77%) were invasive, whereas 3 (23%) were pure DCIS. Only 1 patient died of disease, corresponding to 5- and 10-year actuarial cause specific survival rates of 100% and 99.0%, respectively. Multiple clinical, pathologic, and treatment-related factors were analyzed for association with ipsilateral breast failure or TR/MM. In multivariate analysis, only the absence of pathologic calcifications was significantly associated with ipsilateral breast failure. When specifically analyzed for TR/MM, younger age at diagnosis, number of slides with DCIS, number of DCIS and cancerization of lobules (COL) foci within 5 mm of the margin, and the absence of pathologic calcifications demonstrated a statistically significant association. Close or positive margin status did not significantly predict for either TR/MM (P = 0.14) or ipsilateral breast failure (P = 0.19). CONCLUSIONS: In patients with mammographically detected DCIS treated with BCT, adequate excision of all DCIS prior to RT can result in improved rates of local control. However, margin status may not adequately predict complete tumor extirpation. The volume of DCIS within 5 mm of the margin appears to be a more reliable surrogate for the adequacy of excision. In addition, young patient age and the absence of pathologic calcifications are independent risk factors for the development of local recurrence.     

Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer

Introduction: The aims of the study were to assess the outcome among patients with early breast cancer operated on with wide local excision who developed a subsequent ipsilateral breast tumor recurrence, and to identify risk factors for uncontrolled local disease. Uncontrolled local disease (ULD) was defined as the appearance of clinically manifest invasive adenocarcinoma in the remaining breast or on the ipsilateral chest wall which could not be eradicated with salvage treatment during the period of follow-up (2–18 years). Patients and methods: Eighty-five patients in a cohort of 759 patients, treated for invasive Stage I–II breast cancer with breast-conserving surgery 1976–1985 in Stockholm, with a subsequent ipsilateral breast tumor recurrence (IBTR) were reviewed retrospectively. The majority of the patients were premenopausal (58%), node negative (72%), and had received postoperative radiotherapy (79%). Median follow-up time following breast-conserving surgery was 13 (9–19) years. Multivariate Cox's hazard regression was used in the statistical analysis to identify prognostic factors for ULD. Results: The majority (n = 61) of the IBTR's were located in the original tumor quadrant and showed the same histopathological features as the primary tumor. Salvage mastectomy (n = 65) or reexcision (n = 14) were performed in 79 (93%) of the patients. Twenty-one patients developed ULD. Five years following the diagnosis of IBTR the disease-free survival was 59%, the cumulative incidence for ULD was 24%, and for death in breast cancer 34%. In the cohort of 759 patients, patients who received radiotherapy following the primary breast-conserving surgery had 1% cumulative incidence of ULD following the diagnosis of IBTR compared to 4% among patients that received no postoperative radiotherapy. The cumulative incidence at 5 years of ULD following salvage mastectomy was 12% compared to 33% after salvage reexcision. Patients operated on with breast-conserving surgery with an original tumor size < 15 mm, who were treated with salvage mastectomy for IBTR, had in multivariate analysis the lowest relative risk for ULD. Adjuvant chemotherapy following IBTR treatment did not seem to improve local tumor control. Following the diagnosis of IBTR, 78% (n = 21) of the patients with ULD and/or regional recurrence (n = 27), died of a disseminated breast cancer in contrast to 10% (n = 6) among the remaining 58 patients. Conclusion: Uncontrolled local disease is an important outcome measure following breast-conserving surgery. In this cohort, salvage mastectomy provided a superior local control rate compared to salvage reexcision. A higher although not statistically significant rate of ULD was also seen in patients who had not received postoperative radiotherapy as part of their primary treatment.This revised version was published online in October 2005 with corrections to the Cover Date.     

Significance of margins of excision on breast cancer recurrence

Randomized studies have established wide excision and radiation as an equal alternative to mastectomy in the treatment of breast cancer. The early studies mandated pathologically negative margins for those undergoing radiation. The absolute necessity of free margins is uncertain. We evaluated our experience and outcome with breast-conserving surgery and radiation in relation to margin status. Two hundred sixty patients underwent wide excision for breast-conserving therapy for breast cancer. Reexcision was performed in 149 patients. The initial margin status was correlated with the amount of residual found on reexcision and the effect on local failure. The incidence of residual disease on reexcision in patients with initial gross margin involvement, focal margin involvement, and free margins was 30%. Patients with multiple margin positivity had a 65% incidence of residual disease. Only 9% (14/149) of the reexcised patients had more than 3 mm of residual cancer. This was more likely, but not significant, in those with initial margin involvement (11/100 or 11%) than in those with free margins (3/49 or 6%, p= 0.49). The risk of subsequent local failure was 8% (12/143) in those with initial free margins and 5% (6/117) in those with initial margin involvement. Those who had any residual tumor on reexcision had a nonsignificant risk of local failure (13%) compared to those that had no residual on reexcision (4%). Positive margin on initial excision is only slightly more likely to predict for residual cancer than the finding of negative margins. Routine reexcision of patients with positive margins does not significantly increase the chance of local control in patients who receive breast irradiation.     

Risk of invasive cancer in women with lobular carcinoma in situ of the breast

100 women underwent wide resection for palpable or mammographically detected breast lesions (1 woman had bilateral lesions). Histology excluded invasive cancer, but one or more foci of lobular carcinoma in situ (LCIS) were observed. There have been no recurrences in the 20 women who underwent total mastectomy. In the 12 patients who had a subsequent wide excision and the 68 who received no other treatment 5 presented with an invasive cancer in the same breast at some distance from the LCIS site (median follow-up 58 months). The (observed/expected) rate per 1000 per year is 10.3 for an untreated LCIS. LCIS is therefore a risk factor for invasive carcinoma. Nevertheless this risk does not indicate the use of mutilating procedures and a wait-and-see policy is appropriate.     

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.