Predictors of local recurrence following excision alone for ductal carcinoma in situ

BACKGROUND: The treatment of ductal carcinoma in situ (DCIS) remains controversial, particularly in regard to the selection of patients who may be appropriately treated with wide excision alone. To help identify such patients, the authors assessed prognostic factors for local recurrence in patients with DCIS treated with excision alone. METHODS: The study population consisted of 59 patients diagnosed with DCIS between 1985 and 1990. All had been treated with excision alone, had their histologic slides available for re-review by a study pathologist, and had negative margins of excision on review. The median age at diagnosis was 54 years, and the median follow-up time was 95.5 months. Ninety-six percent presented with mammographic findings only; all patients had a reexcision. The size of the DCIS was assessed by the total number of low-power fields (LPF) in which DCIS was present (median LPF = 5). RESULTS: Ten patients experienced a local recurrence (LR) at 5-132 months (median, 37 months) after excision. The actuarial 5-year LR rate was 10%. Four of the recurrences were invasive carcinomas, and 6 were DCIS. No patients have developed metastatic disease or have died of disease. Lesion size >5 LPF was the only significant prognostic factor for local recurrence on univariate analysis (3% vs. 17% for < or = 5 vs. > or = 5 LPF, P = 0.02) and in proportional hazards models. Although patients with nuclear Grade 3 lesions had a higher LR rate than those with nuclear Grade 1 and 2 lesions (18% vs. 6% and 5%, respectively) and patients with close margins (< or = 1 mm) had a higher LR rate than patients with negative margins (>1 mm) (25% vs. 8%), these differences did not reach statistical significance. Among the 19 cases with margins negative by more than 1 mm, lesion size < or = 5 LPF, and nuclear Grade 1 or 2, there were no LRs; by contrast, the remaining 40 patients had a 5-year actuarial LR rate of 15% (P = 0.08). CONCLUSIONS: Lesion size was the only statistically significant prognostic factor for local recurrence in this series of patients with DCIS treated with excision alone. Other factors, such as margin status and nuclear grade, may also be useful in the identification of patients with DCIS who can be managed with excision alone. However, the most reliable and reproducible method of assessing these factors and the best way to combine them have not been determined.     

Eight-year update of a prospective study of wide excision alone for small low- or intermediate-grade ductal carcinoma in situ (DCIS)

Whether wide excision with margins ≥1 cm is sufficient treatment for small low- or intermediate-grade ductal carcinoma in situ (DCIS) is unclear. This is an updated analysis of a phase II, single-arm, prospective trial testing this hypothesis. A total of 158 patients with low- or intermediate-grade DCIS who underwent wide excision alone (without radiation or tamoxifen) were entered onto the trial from 1995 to 2002. Entry criteria included mammographic extent ≤2.5 cm, predominantly low or intermediate nuclear grade, and excision with final microscopic margins ≥1 cm. Eight-year minimum potential follow-up was required for inclusion in the analysis; the final population comprised 143 patients. Cumulative incidence curves were generated to assess rates of local recurrence (LR) or other events. Median follow-up time was 11 years. Nineteen patients (13 %) had LR as a first event within 8 years. Thirteen LR (68 %) were DCIS only and six (32 %) were invasive. Fourteen (74 %) occurred in the original quadrant. The 10-year estimated cumulative incidence of LR was 15.6 %. The estimated annual percentage rate of LR was 1.9 % per patient-year. With longer follow-up, there remains a substantial and ongoing risk of LR in patients with favorable DCIS treated with wide excision margins without radiation. This information should be useful as patients and clinicians weigh the options of wide excision with and without radiation.     

Outcome and predictive factors of local recurrence and distant metastases following primary surgical treatment of high-grade malignant phyllodes tumours of the breast

AIM: High-grade malignant phyllodes tumour (MPT) is a rare but aggressive breast malignancy and forms approximately 25% of all phyllodes tumours. The aim of the study was to determine parameters that influence outcome in high-grade MPT. METHODS: This study consisted of 48 women diagnosed with high-grade MPT. All patients were treated primarily with surgery by local excision (LE, margins <1 cm), wide local excision (WLE, margins > or =1 cm) or mastectomy. Cox's regression was used for multivariate analysis of the data. RESULTS: The mean patient age was 47 (range 21-85) years and the average tumour size was 7.8 (range 1.5-20) cm. Ten patients were treated with LE, 14 with WLE and 24 with mastectomy. The median follow-up was 9 years (range 5 months-28 years). Local recurrence (LR) occurred in 19 patients (40%) at mean time of 28 (range 5-84) months after primary treatment. Distant metastasis (DM) occurred in 13 (27%) patients at average time of 25.6 (range 6-120) months. LR, subsequent metastatic spread and survival following treatment of MPT were related to tumour size and excision margins, but not to other clinical or histopathological characteristics. CONCLUSION: Tumour size and surgical margins were found to be the principal determinants of LR and DM. Complete surgical excision, by mastectomy if necessary, is important in the primary surgical treatment of high-grade MPT.     

Extent of excision margin width required in breast conserving surgery for ductal carcinoma in situ

BACKGROUND: Breast conserving surgery (BCS) is common practice for unifocal ductal carcinoma in situ (DCIS) less than 4 cm in size, but the extent of tumor free margin width around DCIS necessary to minimize recurrence is unclear. METHODS: Clinical and pathologic details were recorded from all patients with pure DCIS < 4 cm in size, treated with BCS between 1978 and 1997. Histologic margins were measured by using an ocular micrometer. Patients with clear margins (> 1 mm) were divided up into 3 groups for analysis based on margin of normal tissue excised: 1.1-5 mm, 5.1-10 mm, and 10.1-40 mm. RESULTS: There were 66 patients with close margins (< or = 1 mm), of which 25 cases (37.9%) recurred. The recurrence rates for the 3 clear margin groups ranged from 4.5-7.1%. Median followup was 47 months (range 12-197 mos). Risk of recurrence in the group with close margins was greater than the subgroups with clear margins (P < 0.001); no differences in recurrence was seen between the individual subgroups with clear margins. Nuclear Grade 3 was predictive of recurrence (P = 0.03). Following excision alone, the recurrence rate was 18.6%, compared with 11.1% when radiotherapy was given as adjuvant therapy. Women with clear margins following excision had a recurrence rate of only 8.1%. CONCLUSION: After BCS for DCIS, close margins were associated with a high risk of local recurrence. Radiotherapy did not compensate for inadequate surgical clearance.     

Predictors of local recurrence after treatment of ductal carcinoma in situ: a meta-analysis

BACKGROUND: Management of patients with ductal carcinoma in situ (DCIS) is a dilemma, as mastectomy provides nearly a 100% cure rate but at the expense of physical and psychologic morbidity. It would be helpful if we could predict which patients with DCIS are at sufficiently high risk of local recurrence after conservative surgery (CS) alone to warrant postoperative radiotherapy (RT) and which patients are at sufficient risk of local recurrence after CS + RT to warrant mastectomy. The authors reviewed the published studies and identified the factors that may be predictive of local recurrence after management by mastectomy, CS alone, or CS + RT. METHODS: The authors examined patient, tumor, and treatment factors as potential predictors for local recurrence and estimated the risks of recurrence based on a review of published studies. They examined the effects of patient factors (age at diagnosis and family history), tumor factors (sub-type of DCIS, grade, tumor size, necrosis, and margins), and treatment (mastectomy, CS alone, and CS + RT). The 95% confidence intervals (CI) of the recurrence rates for each of the studies were calculated for subtype, grade, and necrosis, using the exact binomial; the summary recurrence rate and 95% CI for each treatment category were calculated by quantitative meta-analysis using the fixed and random effects models applied to proportions. RESULTS: Meta-analysis yielded a summary recurrence rate of 22.5% (95% CI = 16.9-28.2) for studies employing CS alone, 8.9% (95% CI = 6.8-11.0) for CS + RT, and 1.4% (95% CI = 0.7-2.1) for studies involving mastectomy alone. These summary figures indicate a clear and statistically significant separation, and therefore outcome, between the recurrence rates of each treatment category, despite the likelihood that the patients who underwent CS alone were likely to have had smaller, possibly low grade lesions with clear margins. The patients with risk factors of presence of necrosis, high grade cytologic features, or comedo subtype were found to derive the greatest improvement in local control with the addition of RT to CS. Local recurrence among patients treated by CS alone is approximately 20%, and one-half of the recurrences are invasive cancers. For most patients, RT reduces the risk of recurrence after CS alone by at least 50%. The differences in local recurrence between CS alone and CS + RT are most apparent for those patients with high grade tumors or DCIS with necrosis, or of the "comedo" subtype, or DCIS with close or positive surgical margins. CONCLUSIONS: The authors recommend that radiation be added to CS if patients with DCIS who also have the risk factors for local recurrence choose breast conservation over mastectomy. The patients who may be suitable for CS alone outside of a clinical trial may be those who have low grade lesions with little or no necrosis, and with clear surgical margins. Use of the summary statistics when discussing outcomes with patients may help the patient make treatment decisions.     

259 Patients with DCIS of the breast applying USC/Van Nuys prognostic index: a retrospective review with long term follow up

BACKGROUND: The Van Nuys Prognostic Index (VNPI) is a simple score for predicting the risk of local recurrence (LR) in patients with Ductal Carcinoma In Situ (DCIS) conservatively treated. This score combines three independent predictors of Local Recurrence. The VNPI has recently been updated with the addition of age as a fourth parameter into the scoring system (University of Southern California/ VNPI). PATIENTS AND METHODS: Our database consisted of 408 women with DCIS. Applying the USC/VNPI we reviewed retrospectively 259 patients who were treated with breast conserving surgery with or without radiotherapy (RT). Of these patients 63.5% had a low VNPI score, 32% intermediate and 4.5% a high score. In the low score group, the majority of the patients underwent Conservative Surgery (CS) without RT while in the intermediate group, almost half of the patients received RT. Eighty-three percent (83%) of the patients with high VNPI were treated with Conservative Surgery plus RT. Nodal assessment by Sentinel Lymph Node Biopsy was obtained in 32 patients since 2002. RESULTS: Twenty-one Local Recurrences were observed (8%) with a mean follow up of 130 months: sixteen were invasive. No statistically significant differences in Disease Free Survival were reached in all groups of VNPI score between patients treated with Conservative Surgery or Conservative Surgery plus RT. However it was noted that the higher the VNPI score, the lower was the risk of local recurrence in the group treated additionally with RT, even though it was not statistically significant. Further analysis included those patients treated with Conservative Surgery alone and followed up. Disease-free survival (DFS) at 10 years was 94% with low VNPI and 83% in both intermediate and high score (P < 0.05). No significant differences were observed in the subgroups of VNPI. The Local Relapse rate after Conservative Surgery alone, increased with tumor size, margin width, and pathology classification (P < 0,05), while age was not found to be a significant factor. Lesions with only mammographic appearances are associated with lower DFS but it did not reach significance (P = ns), while assumption of estrogenic hormones and familial history of breast cancer are significant factors associated with a higher risk of local recurrence. After multivariate analysis including seven clinical and pathological factors, the only significant predictors of local recurrence remained margin width of surgical excision, previous therapy with estrogens (contraceptives or Hormone Replacement Therapy) and the Van Nuys pathologic classification. The overall survival breast cancer specific was 99% and no differences were observed between groups (P = ns). The comparison of patients treated with a total mastectomy and those conservatively treated showed a significantly better local relapse free survival rate obtained with mastectomy (98.2% vs. 89.7% at 10 years P = 0.02). However, the overall cause-specific survival did not prove any better outcome (98.7% in both groups). Of the 32 patients who underwent a Sentinel Lymph Node Biopsy, four were found to have micrometastases and all of them had a previous Directional Vacuum Assisted Biopsy. CONCLUSIONS: Although in our series there is not a significant difference in LR rates by the parameter of age, the new USC/VNPI is still a simple and reliable scoring system for therapeutic management of DCIS. We did not find any statistically significant advantage in groups treated with the addition of RT. Obtaining wide surgical margins appears to be the strongest prognostic factor for local recurrence, regardless of other pathological factors or the addition of adjuvant radiation therapy. However, only prospective randomized studies can precisely predict the risk of LR of conservatively treated DCIS. The clinical significance of Sentinel Lymph Nodes micrometastases Immuno-Histo-Chemistry-detected found in DCIS patients remains uncertain. However, we hypothesize that the anatomical disruption after preoperative biopsy procedures increases the likelihood of epithelial cell displacement and the frequency of IHC-positive Sentinel Lymph Nodes, both of which are directly proportional to the degree of manipulation.     

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.     

Can we know what to do when DCIS is diagnosed?

Utilizing routine histopathologic parameters obtained from appropriately handled lumpectomy and mastectomy specimens, a rational therapeutic plan based on epidemiologic and outcome-based data can be devised for any patient diagnosed with ductal carcinoma in situ (DCIS). In order to make a sound decision when weighing the current treatment options for DCIS--which include excision alone, excision plus radiation, and mastectomy--the following are mandatory: 1) assurance of an accurate diagnosis, 2) assessment of DCIS size and grade, and 3) careful margin evaluation. Accurate grading of DCIS is critical, since high nuclear grade and the presence of necrosis are highly predictive of the inability to achieve adequate margins, of local recurrence, and of the probability of missed areas of invasion. Margin status is the single most important determinant of local control following breast conservation for DCIS; numerous studies have shown that as the margin width increases, the risk of local failure decreases. The pros and cons of irradiating conservatively treated patients with DCIS should be carefully weighed on a case-by-case basis. Despite the 20-year-old dogma that all patients treated with breast conservation should receive postoperative radiation, a subset of patients who can be successfully treated by excision alone has been identified.     

Differences in the pathologic features of ductal carcinoma in situ of the breast based on patient age

BACKGROUND: Young patient age at diagnosis has been reported as a risk factor for recurrence in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast-conserving therapy (BCT). The authors examined pathologic features of DCIS in three different age groups of patients to identify differences that might explain why young patient age at the time of diagnosis is a risk factor for recurrence. METHODS: Excised specimens from 177 breasts of 172 patients with DCIS treated with BCT were studied. All slides from all specimens were reviewed. Patients were divided into 3 age groups: those age < 45 years, those ages 45-59 years, and those age >/= 60 years. The histologic features that were quantified included most common and highest nuclear grades, DCIS architectural pattern, amount of central necrosis (quartiles), calcifications, amount of DCIS, and number of terminal duct lobular units (TDLUs) with cancerization of lobules (COL) within 0.42 cm of the margin, margin status, and size and volume of excision specimens. RESULTS: Patients age < 45 years at the time of diagnosis more frequently had higher nuclear grade DCIS (highest nuclear Grade 3: 69%, 60%, and 39%; P = 0.003), respectively and central necrosis (72%, 62%, and 44%; P = 0. 01), respectively. Although not statistically significant, younger patients tended to have comedo subtype DCIS more often (31%, 23%, and 19%; P = 0.35), respectively. Younger patients also more often had smaller initial biopsy specimen maximum dimensions (4.3 cm, 5.2 cm, and 5.7 cm; P = 0.004), respectively, with close or positive margins (89%, 61%, and 64%; P = 0.03), and more TDLUs with COL in the 0.42-cm rim of tissue adjacent to the margin (5.2, 3.6, and 1.9; P = 0.23), respectively. No other features including the amount of DCIS when classified as > 50% or > 75% of ducts, calcifications within DCIS ducts, pattern of DCIS involvement, number of slides examined, number of slides with DCIS, and mean number of DCIS ducts near the margin were found to occur more frequently in younger patients. CONCLUSIONS: Younger patients with DCIS may have an increased risk of local recurrence when treated with BCT due to smaller initial excision volumes, a greater proportion of high nuclear grade DCIS, and central necrosis.     

Predictive value of extent and grade of ductal carcinoma in situ in radiologically guided core biopsy for the status of margins in lumpectomy specimens.

AIMS: The correlation between the extent and grade of ductal carcinoma in situ (DCIS) in a core needle biopsy of breast, and the presence of an extensive intraductal carcinoma component (EIC) or positive resection margins in a subsequent mastectomy, has not been adequately addressed in the literature. MATERIALS AND METHODS: Seventy-eight core needle biopsies with mammography and mastectomy correlation (27 total mastectomies, 51 lumpectomies) were reviewed. The extent and grade of DCIS in the biopsies were determined and compared with the mammographic findings and the status of the EIC and margins in subsequent mastectomy specimens. RESULTS: Twenty-four cases of core biopsies with at least three foci of low-grade DCIS or at least two foci of high grade DCIS (group I) corresponded in large part to cases of mastectomy with a positive EIC (20/23 cases, or predictive value of 87%). Nine of 15 cases of lumpectomy in this group were associated with margins positive for or close to (less than 0.1 cm from) carcinoma. Thirty-three cases of core biopsies with one or two foci of low-grade DCIS or one focus of high-grade DCIS (group II) were associated with mastectomies with a limited extent of DCIS. Only four of 22 lumpectomy specimens in this group had margins positive for or close to carcinoma. Twenty-one cases of core biopsies without DCIS (group III) represented all five mastectomy specimens without DCIS, and 16 mastectomies with DCIS and negative EIC. None of the 14 cases of lumpectomy in this group had margins positive for carcinoma. The predictive value for EIC status may be even higher if mammographic findings are used in cases with a low number of foci (two foci of low-grade DCIS or one focus of high-grade DCIS in short biopsy cores). CONCLUSIONS: There was a good correlation between the extent and grade of DCIS in core biopsies and the status of EIC in subsequent mastectomy specimens. Core needle biopsies with at least three foci of low-grade DCIS or at least two foci of high-grade DCIS are associated with a greater likelihood of positive or close margins in subsequent lumpectomies. Core biopsies without DCIS are associated with a greater likelihood of negative margins in subsequent lumpectomies.     

Duct carcinoma in situ: predictors of local recurrence and progression in patients treated by surgery alone

Between 1972 and 1982, 60 patients with histologically proven duct carcinoma in situ (DCIS) without evidence of invasive disease were treated by surgery alone. Treatment was not randomised and was total mastectomy (19), subcutaneous mastectomy (6) or local excision (35). Follow-up was by clinical examination and mammography with a median follow-up of 9 years (range 4-16 years). Twenty-six patients (43%) have recurred locally. The estimated proportion recurrence free at 7 years is 59% (95% CI 46-72%). Local recurrence on the chest wall occurred in one patient having total mastectomy and in the chest wall or nipple in three patients having subcutaneous mastectomy. Twenty-two patients recurred locally in the breast after conservative surgery. The 7-year recurrence-free rates were 94%, 44% and 45% respectively in the three groups. Of those patients who recurred locally 14/26 (54%) did so with invasive disease. Of the 34 who did not develop local recurrence, two developed metastases. The only factor which correlated with local recurrence and invasive local recurrence on multivariate analysis was conservative surgery (hazard ratio 4.71 (1.59-14.0), P = 0.001, and 4.05 (1.00-18.7), P = 0.03, respectively). DCIS can be an aggressive local disease and local excision may be inadequate treatment.     

Giant malignant mammary phyllodes tumor: report of a case and review of the literature

BACKGROUND: To distinguish between a benign and malignant phyllodes tumor before surgery is difficult. Wide excision or mastectomy with adequate free margins is necessary in the case of a malignant phyllodes tumor. However, repairing the skin defect after removal of a giant malignant phyllodes tumor is a great challenge for the breast surgeon. CASE REPORT: We report the case of a 45-year-old Taiwanese woman with a giant malignant phyllodes tumor measuring 30 x 25 x 22 cm. Prior to surgery, we carefully designed a flap to cover the skin defect, following standard mastectomy with at least 2 cm free margins. Postoperatively, the patient recovered well without any wound infection or flap necrosis. During follow-up at our outpatient department, there was no evidence of local relapse or distant metastasis. CONCLUSION: Giant malignant phyllodes tumors can be treated by total mastectomy with adequate free margins, using a flap technique to cover the skin defect.     

Predictors of invasive disease in breast cancer when core biopsy demonstrates DCIS only

BACKGROUND AND OBJECTIVES: Ductal carcinoma in-situ on core biopsy does not preclude invasive disease within the excision specimen, resulting in the need for further axillary surgery. We sought to identify predictors of invasion when DCIS is present on core biopsy. METHODS: From a database of 895 breast cancer patients, patients with DCIS on core biopsy who had subsequent surgical excision were identified. Their excision pathology and preoperative mammography were correlated with risk of invasion. RESULTS: Patients (93) with a preoperative diagnosis of DCIS on core biopsy were identified. On excision, 31 patients (33%) had invasive carcinoma and 13 patients (14%) had microinvasion. A preoperative finding of calcification only on mammogram was associated with DCIS on excision (P = 0.014), whereas the presence of other mammographic features increased the risk of invasion. Size > or =5 cm on excision pathology was associated with increased risk of invasion (P = 0.002). Forty-eight percent (n = 11/23) of those diagnosed by ultrasound-guided core biopsy had frank invasion on excision compared to 21% (n = 12/57) diagnosed by stereotactic techniques (P = 0.017). CONCLUSION: Mammographic features and tumor size can help predict invasion in patients who have DCIS on core biopsy. Patients who have features other than calcification on mammography or have tumor size > or =5 cm should be considered for a sentinel node biopsy.     

Combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer: updated results in a series of 120 patients

PURPOSE: To evaluate our updated data concerning survival and locoregional control in a prospective study of locally advanced noninflammatory breast cancer (LABC) after primary chemotherapy (CT) followed by external preoperative irradiation (RT). METHODS AND MATERIALS: Between 1982 and 1998, 120 patients (75 Stage IIIA, 41 Stage IIIB, and 4 Stage IIIC according to AJCC staging system 2002) were treated by four courses of induction CT with anthracycline-containing combinations followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different locoregional approaches were proposed depending on tumor characteristics and tumor response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. The median follow-up from the beginning of treatment was 140 months. RESULTS: Mastectomy and axillary dissection were performed in 49 patients (with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumor), and conservative treatment in 71 patients (39 achieved clinical complete response or partial response >90% and received additional radiation boost to initial tumor bed; 32 had residual mass < or =3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site). Ten-year actuarial local failure rate was 13% after RT alone, 23% after wide excision and RT, and 4% after mastectomy (p = 0.1). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.002). Ten-year overall metastatic disease-free survival rate was 61%. After multivariate analysis, metastatic disease-free survival rates were significantly influenced by clinical stage (Stage IIIA-B vs. IIIC, p = 0.0003), N-stage (N0 vs. N1-2a, and 3c, p = 0.017), initial tumor size (<6 cm vs. > or =6 cm in diameter, p = 0.008), and tumor response after induction CT and preoperative RT (clinically complete response + partial response vs. nonresponder, p = 0.0015). In the nonconservative breast treatment group, of the 32 patients with no change in clinical tumor size after induction CT, the 10-year metastatic disease-free survival rate was 59% with only one local relapse. Arm lymphedema was noted in 17% (14 of 81) after axillary dissection and in 2.5% (1 of 39) without axillary dissection. Cosmetic results were satisfactory in 70% of patients treated by RT alone and in 51.5% of patients after wide excision and RT. CONCLUSION: Despite the poor prognosis of patients with LABC resistant to primary anthracycline-based regimen, aggressive locoregional management using preoperative RT and mastectomy with axillary dissection offers a possibility of long-term survival with low local failure rate for patients without extensive nodal disease. On the other hand, the rate of local failure seems to be high in patients with clinical partial tumor response after induction CT and breast-conserving treatment combining preoperative RT and large wide excision.     

Risk factors for non-invasive and invasive local recurrence in patients with ductal carcinoma in situ

We aimed to identify clinicopathologic factors associated with local recurrence (LR) in a large population of DCIS patients treated with breast-conserving therapy between 1990–2001 in three health plans. Regression methods were used to estimate relative risks (RR) of LR. Among 2,995 patients, 325 had a LR [10.9 %; median follow-up 4.8 years (range 0.5–15.7)]. After adjusting for health plan and treatment, risk of LR was increased among women <45 years (RR = 2.1, 95 % CI 1.5–2.8), African-Americans (RR = 1.6; 95 % CI 1.1–2.1) and those with DCIS detected because of signs/symptoms (RR = 1.6; 95 % CI 1.2–2.0). After also adjusting for age and diagnosis year, pathologic features associated with increased LR were larger lesion size (RR = 2.9 for ≥20 low power fields of DCIS; 95 % CI 1.6–5.6) and involved (RR = 2.9; 95 % CI 1.6–5.2), or close margins (RR = 2.4; 95 % CI 1.6–3.8). Presentation with symptoms/signs was associated with increased risk of invasive recurrence; while African-American race, larger tumor size, and involved/close tumor margins were more strongly associated with increased risk of DCIS recurrence. Our findings suggest some risk factors differ for non-invasive and invasive LRs and that most factors are only moderately associated with increased LR risk. Future research efforts should focus on non-clinicopathologic factors to identify more powerful risk factors for LR.     

Results of conservative surgery and radiation for mammographically detected ductal carcinoma in situ (DCIS)

: The role of conservative surgery and radiation for mammographically detecged ductal carcinma in situ (DCIS) is controversial. In particular, there is little date for outcome with radiation in a group of patients comparable to those treated with local excision and surveillance (mammographic calcifications ≤2.5cm, negative resection margins, negative postbiopsy mammogram). This study reports outcome of conservative surgery and radiation for mammographically detected DCIS with an emphasis on results in patients considered candidates for excision alone.

: From 1983 to 1992, 110 women with mammographically detected DCIS (77% calcifications ± mass) and no prior history of breast cancer underwent needle localization and biopsy with (55%) or without a reexicision and radiation. Final margins of resection were negative in 62%, positive 7%, close 11%, and unknown 20%. The median patient age was 56 years. The most common histologic subtype was comedo (54%), followed by cribriform (22%). The median pathologic tumor size was 8 mm (range 2 mm to 5 cm). Forty-seven percent of patients with calcifications only had a negative postbiopsy mammogram prior to radiation. Radiation consisted of treatment to the entire breast (median 50.00 Gy) and a boost to the primary site (97%) for a median total dose of 60.40 Gy.

: With a median follow-up of 5.3 years, three patients developed a recurrence in the treated breast. The median interval to recurrence was 8.8 years and all were invasive cancers. Two (67%) occurred outside the initial quadrant. The 5- and 10-year actuarial rates of recurrence were 1 and 15%. Cause-specific survival was 100% at 5 and 10 years. Contralateral breast cancer developed in two patients. There were too few failures for statistical significance to be achieved with any of the following factors: patient age, family history, race, mammographic findings, location primary, pathologic size, histologic subtype, reexcision, or final margin status. However, young age, positive or close margins, and the presence of a mass without calcifications had a trend for an increased risk of recurrence. There were no recurrences in the subset of 16 patients who would be candicates for surveillance by Lagio's criteria.

: For selected patients, conservative surgery and radiation for mammographically detected DCIS results in a low risk of recurrence in the treated breast and 100% 5- and 10-year cause-specific survival. Improved mammographic and pathologic evaluation results in better patient selection and reduced the risk of the subsequent appearance of DCIS in the biopsy site. The identification of risk factors for an ipsilateral invasive breast recurrence is evolving.     

Influence of margin status and radiation on recurrence after radical hysterectomy in Stage IB cervical cancer

PURPOSE: To examine the relationship between margin status and local recurrence (LR) or any recurrence after radical hysterectomy (RH) in women treated with or without radiotherapy (RT) for Stage IB cervical carcinoma. METHODS AND MATERIALS: This study included 284 patients after RH with assessable margins between 1980 and 2000. Each margin was scored as negative (> or =1 cm), close (>0 and <1 cm), or positive. The outcomes measured were any recurrence, LR, and relapse-free survival. Results: The crude rate for any recurrence was 11%, 20%, and 38% for patients with negative, close, and positive margins, respectively. The crude rate for LR was 10%, 11%, and 38%, respectively. Postoperative RT decreased the rate of LR from 10% to 0% for negative, 17% to 0% for close, and 50% to 25% for positive margins. The significant predictors of decreased relapse-free survival on univariate analysis were the depth of tumor invasion (hazard ratio [HR] 2.14/cm increase, p = 0.007), positive margins (HR 3.92, p = 0.02), tumor size (HR 1.3/cm increase, p = 0.02), lymphovascular invasion (HR 2.19, p = 0.03), and margin status (HR 0.002/increasing millimeter from cancer for those with close margins, p = 0.03). Long-term side effects occurred in 8% after RH and 19% after RH and RT. CONCLUSION: The use of postoperative RT may decrease the risk of LR in patients with close paracervical margins. Patients with other adverse prognostic factors and close margins may also benefit from the use of postoperative RT. However, RT after RH may increase the risk of long-term side effects.     

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.     

Ductal carcinoma in situ of the breast

Ductal carcinoma in situ (DCIS) of the breast is a noninvasive form of breast cancer that has increased in incidence over the past several decades secondary to screening mammography. DCIS now represents 20–30% of all newly diagnosed cases of breast cancer. Patients with DCIS typically present with an abnormal mammogram, and diagnosis is most commonly obtained with an image-guided biopsy. Historically, mastectomy was considered the primary curative option for patients with DCIS. However, treatment of DCIS continues to evolve, and now treatment strategies also include breast-conserving therapy, which consists of local excision followed by radiation therapy or local excision alone. Multiple randomized trials have confirmed a decrease in ipsilateral breast tumor recurrence in patients treated with local excision followed by radiation therapy compared with local excision alone. Ongoing clinical trials attempt to identify a subgroup of DCIS patients at low risk for recurrence who may not benefit from radiation therapy. In addition, because the majority of ipsilateral breast tumor recurrences occur near the original primary tumor site, partial breast irradiation is currently under investigation as a treatment option for DCIS patients. Randomized trials have shown tamoxifen can reduce the risk of ipsilateral and contralateral breast tumor recurrences while the role of aromatase inhibitors is the subject of current clinical trials. DCIS represents a complex pathologic entity, and treatment optimization requires a multidisciplinary approach.     

乳腺叶状肿瘤17例诊疗分析

目的:探讨乳腺叶状肿瘤的治疗原则和影响预后因素。方法:对经手术和病理诊断确诊的17例乳腺叶状肿瘤的临床资料进行回顾性分析。结果:17例患者中良性叶状肿瘤9例,交界性叶状肿瘤5例,恶性3例。行局部肿块切除7例,单纯乳房切除术6例,改良根治术3例,姑息性肿块切除术1例。其中随访13例,平均随访时间21(5~84)个月,1例行乳腺癌改良根治术后2.5年死于远处转移,2例行局部肿块切除术后复发。结论:乳腺叶状肿瘤的预后与手术方式有关,良性和交界性应首选扩大区段切除术,切除肿瘤边缘不少于2cm;复发的交界性和恶性应尽早行单纯乳房切除术。