Local Recurrence Breast Research Articles

53: PhaseI/II Study of Partial Breast Brachytherapy in Patients Who Have Previously Received External Beam Radiation Therapy (RT) to the Breast

Mastectomy is the most widely accepted treatment for managing local recurrence or new breast cancer in patients who have previously received RT to the breast. With accumulating evidence supporting partial breast irradiation, we embarked on a Phase I/II study to evaluate the role of brachytherapy for patients presenting with either a local breast recurrence after lumpectomy and RT or a new breast cancer diagnosed in women who had previously received mantle irradiation.

Long-term follow-up of a randomised trial designed to determine the need for irradiation following conservative surgery for the treatment of invasive breast cancer

Four hundred consecutive patients aged under 70 years diagnosed with a clinical T1 or T2 breast cancer were randomised to receive post-operative radiotherapy (n = 208) or not (n = 192), and monitored to record all local recurrences, distant recurrences and deaths for up to 20 years (median 13.7 years). All patients were treated by wide local excision and adjuvant therapy [estrogen receptor (ER) positive: tamoxifen; ER negative: CMF chemotherapy]. Kaplan–Meier and log-rank test methods were used to estimate and compare survival and recurrence. The 20-year Kaplan–Meier rates for local breast recurrence were 28.6% [95% confidence interval (CI) 19.6% to 37.6%] for radiotherapy and 49.8% (95% CI 40.8% to 58.9%). There was no significant difference between the two groups with regard to disease-free or overall survival. The hazard ratio for death among women who received radiation, as compared with those that did not, was 0.91 (95% CI 0.64–1.28; P = 0.59). Therefore, post-operative radiotherapy produced a clear-cut reduction in locoregional recurrence 0.45 (0.31–0.64; P = 0.0001), but did not influence the incidence of distant metastases or time of death. However, of the 119 patients who had a local recurrence, 51 (42.8%) had a distant recurrence, whereas of the 281 without local recurrence only 59 (21%) ever had a distant recurrence. A Cox's regression analysis with local recurrence as a time-dependent variable showed a risk ratio of 5.28 (P < 0.0001). This strong relationship is dependent on the intensity of post-treatment follow-up and investigation.

Doppler US with perfusion software and contrast medium injection in the early evaluation of radiofrequency in breast cancer recurrences: A prospective phase II study

Introduction The aim of this study was to determine the efficacy of Doppler ultrasonography (US) with perfusion software and contrast agent injection (DUPC) during radiofrequency (RF) treatment of local recurrent breast cancer. Materials and Methods Ten patients were included in this monocentric prospective phase II study. DUPC was performed for each patient the day before treatment and immediately after RF in the operating suite. RF ablation was followed by a total mastectomy. The results of DUPC were compared to the histologic analysis of the operative specimen. Results Before RF, contrast uptake exceeded 70% in 5 lesions and was less than 50% in 5 lesions. Immediately after RF, no vascularization was detected with DUPC in 9 of the 10 lesions. Contrast uptake attaining 30% was depicted in the remaining lesion. At histologic analysis, complete tumour destruction was confirmed in 7 of the 10 operative specimens. Conclusion In this study, DUPC is highly efficient and better adapted for the confirmation of tumour destruction in tumours that are hypervascularised before RF compared to hypovascularised lesions.

93 oral Predicting local recurrence in breast conserving therapy by gene expression profiling

93 oral Predicting local recurrence in breast conserving therapy by gene expression profiling

574 poster Simultaneous radio-chemotherapy (RCT) of local recurrent breast cancer (RBC) and inoperable primary breast cancer (PBC) — Experiences with two schedules containing Taxans

574 poster Simultaneous radio-chemotherapy (RCT) of local recurrent breast cancer (RBC) and inoperable primary breast cancer (PBC) — Experiences with two schedules containing Taxans

Phase I-II trial of hypofractionated whole breast radiation therapy for ductal carcinoma in situ (DCIS)

To determine the feasibility of hypofractionated breast radiotherapy as part of breast preservation in selected women with DCIS. Intriguing data supporting the use of hypofractionated radiation therapy in the treatment of invasive breast cancer was recently published. (Whelan TJ et al., JNCI, 2002). This Canadian randomized trial compared 42.5 Gy in 16 fractions to 50 Gy in 25 fractions in node-negative invasive breast cancer. No significant differences in 5-year local breast recurrence, disease-free survival, overall survival, and cosmetic outcome were detected between the two arms.

Phase I-II trial of hypofractionated whole breast radiation therapy for ductal carcinoma in situ (DCIS)

To determine the feasibility of hypofractionated breast radiotherapy as part of breast preservation in selected women with DCIS. Intriguing data supporting the use of hypofractionated radiation therapy in the treatment of invasive breast cancer was recently published. (Whelan TJ et al., JNCI, 2002). This Canadian randomized trial compared 42.5 Gy in 16 fractions to 50 Gy in 25 fractions in node-negative invasive breast cancer. No significant differences in 5-year local breast recurrence, disease-free survival, overall survival, and cosmetic outcome were detected between the two arms.

Relation between the method of detection of initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma.

Mammography and physical examination are routine methods for the detection of ipsilateral local recurrence and contralateral breast carcinoma in patients initially undergoing breast conservation treatment. The current study reports the relation between the method of detection of the initial breast carcinoma and the method of detection of subsequent ipsilateral local recurrence and contralateral breast carcinoma. A retrospective review was performed of the records of female patients with initial American Joint Committee on Cancer (AJCC) Stage I and II invasive breast carcinoma who developed ipsilateral local recurrence or contralateral breast carcinoma after breast conservation treatment. The method of detection of local recurrence in the ipsilateral breast and the method of detection of contralateral breast carcinoma were compared with the method of detection of the primary tumor. There were 125 ipsilateral breast local recurrences and 71 contralateral breast carcinoma cases detected. Of the 125 recurrences in the ipsilateral breast, 38% (48 recurrences) were detected by mammography only, 37% (46 recurrences) were detected by physical examination only, and 25% (31 recurrences) were detected by both methods. Of the 71 contralateral breast carcinoma cases, 53% (38 cases) were detected by mammography only, 23% (16 cases) were detected by physical examination only, and 24% (17 cases) were detected by both methods. When the primary tumors were detected by mammography only, 21% of the local recurrences (3 of 14 local recurrences) and 19% of the contralateral breast carcinoma cases (4 of 21 cases) were detected by physical examination only. When the primary tumors were detected by physical examination only, 24% of the local recurrences (14 of 58 local recurrences) and 42% of the contralateral breast carcinoma cases (8 of 19 cases) were detected by mammography only. When stratified by the interval between diagnosis of the primary tumor and ipsilateral local recurrence or contralateral breast carcinoma (< or = 5 years vs. > 5 years) or age of the patient at the time of ipsilateral breast recurrence or contralateral breast carcinoma (age < or = 49 years vs. age > or = 50 years), both breast examination and mammography were found to be important in the detection of locally recurrent tumor and contralateral breast carcinoma in each subgroup of the patients, regardless of the method of presentation of the primary tumor. Both mammography and physical examination were found to be significant in the detection of locally recurrent tumor in the ipsilateral breast and in the detection of contralateral breast carcinoma, regardless of the method of detection of the primary tumor.

Recidivas locorregionales tras el tratamiento conservador del cáncer de mama en estadios I y II

Since 1992 conservative treatment of breast cancer (stage I and II: clinical TNM) has been established as an alternative to mastectomy in our hospital. The aim of this retrospective study was to analyse locoregional recurrence features and to compare prognosis with regard to to site of recurrence. Between 1987 and 1993, 489 patients with breast cancer (stages I and II) were treated with conservative surgery and radiation therapy at the Hospital Sant Pau of Barcelona. Mean follow-up was 58.8 months [between 12-144]. 35 patients developed locoregional recurrence. We considered two groups: local recurrence in breast only; and locoregional recurrence such as nodal recurrence with or without simultaneous breast recurrence. Diagnosis was confirmed by histopathologic analysis. An extensive study was performed in all patients to rule out distant metastasis. Last follow-up was December 1999. The locoregional recurrence rate after conservative treatment was 7.5% and that of local recurrence was 3.06%. Recurrences were diagnosed in 80% of patients by physical examination, while 20% of patients had noticed the tumor recurrence themselves. Histologic grade III tumors had a higher number of locoregional recurrences than local recurrences (p = 0.030). Locoregional recurrences had lower overall survival rate (p = 0.0005), lower disease-free survival rate (p = 0.0012) and shorter time period without distant metastasis (p < 0.0005) than local recurrences. Most recurrences were diagnosed by clinical examination during follow up. Histologic grade III was related to locoregional recurrences. Local recurrences had a better prognosis than locoregional recurrences.

Results of breast-conserving therapy for early stage breast cancer: Kyoto University experiences.

This study evaluated the results of breast-conserving therapy (BCT). Nine hundred six patients who underwent BCT at our hospital between November 1987 and February 1998 were analyzed. The mean age was 48 years. According to the Union Internationale Contre le Cancer 1997 classification system, stages 0, I, IIA, IIB, IIIA, and IIIB were 37, 400, 344, 117, 7, and 1, respectively. Radiation therapy consisted of 50 Gy to the ipsilateral whole breast. Boost irradiation of 10 Gy was administered to 186 of 231 patients with close or positive margins. Nearly all patients received adjuvant chemohormonal therapy with tamoxifen and 5-fluorouracil or its derivatives for 2 years. The minimum and median follow-up periods were 18 and 52 months, respectively. The 5-year overall survival, cause-specific survival, local recurrence-free survival, and disease-free survival rates were 97.3%, 98.4%, 98.1%, and 91.5%, respectively. Local recurrence in preserved breast occurred in 20 patients 7 to 86 months after surgery. Multivariate analysis revealed that the most predictive factor for disease-free survival rates and distant failures was the number of pathologically positive lymph nodes (p < 0.0001), and that the factor for local failure was marginal status (p = 0.005). This study demonstrated that BCT was suitable for the treatment of early-stage breast cancer with its reasonable survival rates and acceptable toxicity.

Evaluation of predictive factors for local tumour control after electron-beam-rotation irradiation of the chest wall in locally advanced breast cancer

Background and purpose: Different radiotherapy techniques are being used for chest wall irradiation after mastectomy. We review our results with the electron-beam-rotation technique in a series of 130 high risk breast cancer patients. The main end point of the study was local tumour control; secondary end points were disease free survival, and overall survival, as well as acute and late side effects. Material and methods: From January 1990 to June 1995, 89 patients underwent electron-beam-rotation irradiation of the chest wall after primary mastectomy and axillary lymph node dissection (group I) and 41 patients after excision of local recurrent breast cancer (group II) with 4×2.5 Gy/week to 50 Gy total dose (4–12 MeV electrons depending on the thickness of the chest wall). In addition, irradiation of local-regional lymph nodes and/or a local boost of 10 Gy were applied dependent on the resection and node status. Results: After a median follow up of 29 months (65% stadium III/IV) the 3 year local tumour control, disease free survival, and overall survival were 73%, 47%, and 75%, respectively. Local control in group I was 78% versus 60% in group II. Significant predictors for local tumour control, disease free survival, and overall survival were resection status (R0 versus R1/2) and estrogen receptor status (positive versus negative). In group I, tumour grading (GI-IIa versus GIIb-III) and estrogen receptor status were found to be additional significant prognostic factors for complete resected tumours. Five patients developed symptomatic pneumonitis (< 4%) and one patient developed a chronic fistula at the resection. A significant correlation between the degree of acute skin reaction and persistent pigmentation was observed. Conclusion: In high risk breast cancer patients postoperative irradiation with the electron-beam-rotation technique of the chest wall is an effective therapy resulting in 78% local tumour control at 3 years for locally advanced breast cancer and 60 % for recurrent disease. The rate of acute and late toxicity is low. The degree of acute skin reaction correlates with the degree of persistent pigmentation.

Local resection and brachytherapy confined to the lumpectomy site for early breast cancer: a pilot study.

The commonest site of local breast recurrence after breast conservation surgery is the primary tumor bed. We have tested the feasibility of outpatient high dose rate brachytherapy to the primary tumor bed as the only radiation. Our technique relies on the placement of surgical clips to mark the tumor bed. Between March 1992 and January 1996, 39 patients with clinical T1 T2 breast cancer were enrolled in this pilot study. The first 13 patients had intraoperative implantation of the breast. The remaining 26 patients had outpatient postoperative implantation under general anesthesia (2 patients) or local anaesthesia (24 patients). High dose rate brachytherapy was given twice daily at least 6 hours apart for a total dose of 37.2 Gy in 10 fractions over 5-7 days. Three patients had mild clinical cellulitis responding to oral antibiotics. One patient had a small sinus in the lumpectomy scar requiring local excision to heal. Four patients developed fat necrosis at the lumpectomy site at 4 (1 patient), 13 (1 patient), and 18 months (2 patients) post radiotherapy. Patient rated satisfaction with treatment was high. At a median followup of 20 months, one infield local recurrence has been salvaged by wider resection and postoperative conventional external beam radiation. Except for fat necrosis, which may be associated with this technique, complications have been minimal. Outpatient implantation under local anesthesia is feasible. Longer followup is required to establish the local control rates.

2005 The effect of delay in initiating radiotherapy post-lumpectomy on local breast recurrence

2005 The effect of delay in initiating radiotherapy post-lumpectomy on local breast recurrence

Ipsilateral breast tumor recurrence postlumpectomy is predictive of subsequent mortality: Results from a randomized trial

Purpose : To determine whether ipsilateral breast tumor recurrence (IBTR) postlumpectomy was independently predictive of distant relapse and mortality in women with node negative breast cancer. Methods and Materials : A randomized trial was conducted in Ontario between 1984 and 1989, in which 837 women with node negative disease who had undergone lumpectomy and axillary dissection were randomized to either postoperative radiation (40 Gy in 16 fractions to the whole breast, followed by a boost of 12.5 Gy in five fractions to the primary site), or no further treatment. A Cox proportional hazards regression analysis was performed for the endpoints mortality and distant relapse using the fixed covariates, treatment, age, tumour size, estrogen receptor status, progesterone receptor status, and nuclear grade; and the time dependent variable IBTR. Results : The analysis was based on 799 patients for which all fixed covariate data was available. Median follow-up was 66 months. The cumulative rate of IBTR at 5 years was significantly greater for the no treatment group compared to the radiation group; 30% vs. 8% respectively ( p < 0.0001). No difference was detected in overall survival between the treatment groups ( p = 0.45). Significant independent predictors for mortality were nuclear grade, high vs. medium or low (relative risk (RR) = 2.28, p = 0.0001); and tumor size ≥ 2 cm. vs. < 2 cm. (RR = 1.64, p = 0.01). In addition, IBTR predicted increased mortality (RR = 2.18, p = 0.0006). Similar results were observed for distant relapse. An IBTR within 1 year of surgery was associated with a higher risk of distant relapse and mortality. Conclusion : Local breast recurrence following lumpectomy is associated with an increased risk of distant relapse and death.

Overview of the biology and management of ductal carcinoma in situ of the breast.

Ductal carcinoma in situ of the breast (DCIS) is an early, noninvasive stage of breast malignancy that arises from ductal epithelium and has an especially favorable prognosis. Its biologic characteristics are consistent with a direct precursor to invasive carcinoma, which develops in the majority of cases if left untreated, generally within 10 years of diagnosis. Mammography has resulted in a substantial increase in its diagnosis, as well as a change in its presentation from large, palpable masses to nonpalpable lesions manifested primarily as microcalcifications. The same treatment options are available for DCIS as for invasive breast carcinoma, and there is also a limited role for wide local excision alone in incidental lesions. Most cases of DCIS currently are treated effectively by lumpectomy and radiation therapy, although the fact that 50% of all local breast recurrences are invasive lesions may affect survival adversely. Mastectomy is associated with the best survival rates and should be performed on any patient with factors known to pose a high risk of locoregional recurrence. There are still many outstanding issues to be resolved by further study before the intriguing potential of this disease can be realized fully.

The effect of advanced age on the efficacy of radiation therapy for early breast cancer, local prostate cancer and grade III–IV gliomas

Purpose : This study was undertaken to determine the effect of advanced age on radiation therapy outcomes for early breast cancer, local prostate cancer and Grade 3–4 gliomas of the brain. Methods and Materials : Radiation therapy outcomes for three malignancies (N = 1,401) were determined for a geriatric cancer population defined as 70 years of age or older and compared to a non-geriatric cancer population defined as less than 70 years of age. The three patient groups studied were: (a) primary breast cancer patients with clinical Stage I or II disease treated with lumpectomy and radiation therapy (N = 994), (b) local prostate cancer patients with Stage A2, B, or C disease treated with radical radiation therapy (N = 294), and (c) patients with Grade 3–4 gliomas of the brain treated with high dose radiation therapy (N = 113). Results : For Stage I and 11 breast cancer, there was no statistically significant difference in the overall 10-year survival rates (63% vs. 73%), 10-year cause-specific disease-free survival rates (70% vs. 63%), and 10-year local breast recurrence free survival rates (76% vs. 79%) comparing the geriatric cancer population to the non-geriatric cancer population. For local prostate cancer, there was no statistically significant difference in the 10-year survival rates (38% vs. 41%) or in the 10-year cause-specific disease-free survival rates (58% vs. 52%) in the geriatric population compared with the non-geriatric population. On the other hand, the use of high dose radiation therapy for malignant gliomas resulted in statistically significant inferior 1-year (18% vs. 38%) and 2-year (0% vs. 10%) survival rates for the geriatric population versus the non-geriatric population. Conclusion : This study strongly supports the use of standard radiation therapy programs for early breast and prostate cancer patients age 70 years or more. However, our study raises questions about the efficacy of radiation therapy in patients over the age of 70 years with Grade 3–4 gliomas.

Local breast recurrence (lbr) post-lumpectomy is predictive of subsequent mortality: Results from a randomized trial

Local breast recurrence (lbr) post-lumpectomy is predictive of subsequent mortality: Results from a randomized trial

Breast conservation therapy in patients with mammographically undetected breast cancer.

The authors reviewed their experience with 542 patients with breast cancer who were treated with conservative surgery and radiation therapy (CSRT) and analyzed the outcome in those patients whose tumors could not be detected with mammography. Fifty-five of the patients (10.1%) had a palpable, pathologically confirmed breast carcinoma and a negative preoperative mammogram. Routine follow-up included annual mammography and physical examination. The local recurrence, 5-year actuarial survival, and 5-year disease-free survival rates for these 55 patients did not differ significantly from those for patients with positive mammograms. There were six cases of local breast recurrence in this subgroup. Four of five cases were visible on mammograms (one patient did not undergo mammography at the time of recurrence); two of the cases were detected with mammography alone following physical examination with negative results. The authors conclude that patients with palpable but mammographically occult early-stage breast cancer are suitable candidates for CSRT and that mammography is a mandatory part of follow-up of conservatively treated patients.

The effect of systemic adjuvant chemotherapy on local breast recurrence in node positive breast cancer patients treated by lumpectomy without radiation

A randomised trial has previously been repeated in which 437 women with node positive breast cancer received either a 12-week chemohormonal regimen consisting of cyclophosphamide, methotrexate, fluorouracil, vincristine, prednisone, adriamycin and tamoxifen or 36 weeks of CMFVP. The present analysis concerns the local recurrence rates for the 122 lumpectomy patients who did not receive breast irradiation. The cumulative rate of local breast recurrence was greater in the 12-week than the 36-week group, P = 0.02. Similarly, in the lumpectomy patients, the cumulative rate of distant recurrence was greater in the 12-week than the 36-week group, P = 0.04. In conclusion, our results suggest that adjuvant chemotherapy impacts on local breast recurrence in a similar manner to other sites in Stage II breast cancer patients treated by lumpectomy without radiation. Despite the use of a conventional 36-week adjuvant chemotherapy regimen, the local breast recurrence rate was substantial.

Conservative management of intraductal carcinoma (DCIS) of the breast. Collaborating NSABP investigators.

Seventy-six patients with intraductal carcinoma (DCIS) of the breast have been observed for 83 months (range 50-141) following treatment by lumpectomy (L) only (21), L and breast irradiation (XRT) (27), or mastectomy (28). All represented examples of DCIS retrieved after pathologic examination of a much larger cohort of patients with stage I and II invasive breast cancer enrolled in NSABP protocol 6. Local breast recurrences were similar for women with DCIS and those from this cohort at a similar period of follow-up with invasive cancer treated by L only (43% vs. 39%) and L + XRT (7% vs. 10%). The presence of moderate/marked comedonecrosis was suggestively related to local breast recurrence (P = .07). This latter was significantly reduced for patients receiving post L XRT (P = .01). All local breast recurrences in this study and 29 of 31 recorded by others occurred at or close to the site of extirpation of the index cancer minimizing multicentricity as a contraindication for the conservative surgical treatment of DCIS. Survival rates which were similar for patients with DCIS regardless of form of local treatment were better than that observed for negative node patients with invasive cancer enrolled in protocol 6. Thus, DCIS is a less, not more, ominous disease than invasive cancer. This and other features of its natural history indicate that it would be a contradiction to treat invasive cancer but not DCIS conservatively.