Uncontrolled local recurrence after treatment of breast cancer with breast conservation

Three hundred fifty-six patients with early (Stage I and II) breast cancer and 55 with advanced (Stage III and IV) breast cancer were treated between 1979 and 1985 with a consistent policy of breast conservation irrespective of tumor site, size, or histologic features. Only three patients underwent primary mastectomy (Stage III), and the remainder were treated either by wide local excision and postoperative radiotherapy (357 cases) or by needle biopsy and primary irradiation (51 cases). A total of seven of 356 (2%) Stage I and II patients have developed uncontrolled local or nodal recurrence at a median follow-up of 5 years, and nine of 55 (16%) of Stage III and IV patients. Of the 62 Stage I and II patients who have died, seven (11%) have died with uncontrolled locoregional disease. Of the 22 Stage III and IV patients who have died, eight (36%) have died with uncontrolled locoregional disease. Although the majority of local recurrences within the conserved breast could be salvaged by secondary surgery (37/38 Stage I and II patients), the development of chest wall or nodal recurrence was usually associated with the appearance of distant metastases and a poor prognosis. Data on uncontrolled local recurrence should be given in all studies of breast cancer treatment, since it represents an important end-point of therapy and a difficult clinical problem.     

Analysis of local recurrence after breast conservative treatment for invasive breast cancer: a single institution cohort

In a group of 900 patients treated for carcinoma of the breast, we evaluated patient-, tumour- and treatment-related parameters, predicting the success or failure of conservative treatment for invasive breast cancer. Thirty-one patients developed local recurrences which were detected within 0.1-12.1 years after treatment of the primary tumour (with a median of 6.2 years), providing a risk of 2% at 5 years and 9% at 10 years. The locally recurrent tumours and their original primary tumours of 28 patients could be retrieved from the pathology laboratory archives. These 28 tumours of the recurrence group (RG) were matched with tumours without local recurrence, the non-recurrence group, for age at time of diagnosis, duration of follow-up and T- and N-stage. The tumours were studied for type and grade of invasive tumour including the in situ component and involvement of surgical margins. In addition, the expression of cell-cycle proteins, p53, Ki-67 (MIB-1) and BCL-1, as well as HER-2/ neu oncoprotein, estrogen and progesterone receptor were investigated. We found a mean age at diagnosis for the RG of 50 years, and the mean age at time of diagnosis for the whole group of 900 patients was 56 years (p=0.003). Thirty-nine percent of the RG had a positive surgical margin, which was the case for only 18% in the control group (p=0.09). The presence of the in situ component was also correlated with increased local recurrence (p=0.022). Furthermore, local recurrence was also associated with a significantly increased occurrence of distant metastases (p=0.001). We conclude that breast conservative treatment is safe with a low local recurrence rate.     

Size of invasive breast cancer and risk of local recurrence after breast-conservation therapy

Risk of local recurrence is one important factor that determines a woman's suitability for breast-conservation therapy. With the evolution of oncoplastic surgery, tumours of a size that traditionally require mastectomy may be treated by breast conservation and partial breast reconstruction. This article reviews the evidence relating to tumour size as a risk factor for local recurrence to assess whether this change in practice is appropriate. A literature review through Medline and Pubmed was performed. All pathological studies analysing tumour size as a predictor of multifocality and all randomised trials and large case series of breast conservation including tumours larger than 2 cm were reviewed and critically interpreted. Pathological studies report consistent evidence that tumour size is not predictive of multifocality. Randomised trials and clinical series of breast conservation report conflicting evidence relating to tumour size as a risk factor for local recurrence, although most studies report no association. Evidence relating to cancers over 3 cm is limited. There is little evidence to justify the use of tumour size alone as an exclusion criterion for breast-conservation therapy. A registration study of patients with cancers larger than 3 cm treated by breast conservation with or without partial breast reconstruction is proposed.     

Long-term prognosis of patients with axillary recurrence after axillary dissection for invasive breast cancer.

AIM: To investigate the long-term prognosis of patients with axillary recurrence after axillary dissection for invasive breast cancer and describe the long-term survivors. METHODS: Between 1984 and 1994, 4669 patients with invasive breast cancer underwent axillary dissection in eight community hospitals in the south-eastern part of The Netherlands. Using follow-up data of the population-based Eindhoven Cancer Registry, 59 patients with axillary recurrence were identified. RESULTS: The median interval between treatment of the primary tumour and diagnosis of axillary recurrence was 2.6 years (range 0.3-10.7). The median length of follow-up after diagnosis of axillary recurrence was 11.1 years (5.7-15.6). Distant metastases occurred in 38 of the 59 patients. The 5- and 10-year distant recurrence-free survival rates were 39% (95% CI: 25-52%) and 29% (95% CI: 16-42%). CONCLUSIONS: Axillary recurrence following axillary dissection is associated with a high rate of subsequent distant metastasis and poor overall prognosis but is not always a fatal event. Our results show that it is possible to cure about one-third of the patients.     

Pathological features predictive of local recurrence after management by conservation of invasive breast cancer: importance of non-invasive carcinoma.

The pathological features of 236 clinical stage I and II invasive breast carcinomas treated by conservation were reviewed. On follow-up (minimum 2 years) 13 patients (6%) have developed breast relapse, 10 (4%) regional lymph node relapse and 26 (11%) distant metastases. Nineteen patients have died from breast carcinoma. On univariate analyses lymph node metastases, increasing amounts of non-invasive carcinoma and multiple foci of invasion were significant risk factors for breast relapse. A Cox's multivariate analysis showed the first two of these to be independently significant. The results are in agreement with other published series and confirm that assessment of non-invasive carcinoma is important. The study compares simple quantitation with the original method reported to define cases with an "extensive intraduct component".     

The prognosis of patients with local recurrence more than five years after breast conservation therapy for invasive breast carcinoma.

AIMS: The increasing use of breast-conserving therapy (BCT) and the rising incidence and improved prognosis of early breast are causing a substantial increase in the absolute number of patients with a late local recurrence following BCT. This study examined the characteristics and the prognosis of patients with a local recurrence occurring more than 5 years after BCT. METHODS: In the period 1982-1997, 3280 patients with invasive breast cancer underwent breast-conserving therapy in one of the eight community hospitals in the South-eastern part of The Netherlands. Of these patients, 98 developed a local recurrence in the breast more than 5 years after BCT. RESULTS: Eighty-five of the 98 recurrences were invasive, 12 were purely in situ and for one patient this information was not available. The 5 years distant recurrence-free survival rate of 85 patients with a late invasive local recurrence was 68% (95% confidence interval [CI], 56-80) and significantly better than the rate of 41% (95% CI, 33-48) in an existing cohort of 173 patients with invasive recurrence within 5 years after BCT (p=0.007). Local excision of the recurrence was followed by a significantly lower local control rate than salvage mastectomy (50 vs 89%; p=0.004). CONCLUSION: The prognosis of patients with a local recurrence more than 5 years after BCT is significantly better than of patients with local recurrence within 5 years after BCT.     

Biopsy findings after breast conservation therapy for early-stage invasive breast cancer

PURPOSE: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. METHODS AND MATERIALS: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. RESULTS: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median time to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if >or=51 years, 57% if 36-50 years, and 83% if 180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p >or= 0.15). CONCLUSION: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.     

Long-term prognosis of patients with local recurrence of breast cancer

From 1985 to 2002, 22 patients with local recurrence after radical mastectomy have been treated in our hospital. Resection was possible in 9 patients. We evaluated long-term prognosis of the 9 patients. The observation interval from first recurrence was 17-207 months (median 91.5 months). Five of the 9 experienced recurrence again. Opposite axillary lymph node metastasis was observed in 2, bone metastasis in 1, liver metastasis in 1, and lung metastasis in 1. Disease free interval (DFI) until the first recurrence of patients with a second recurrence was 69-100 months (median 90 months). The interval from first recurrence to second recurrence was 46-108 months (median 60 months). Each second recurrence occurred within double the DFI until the first recurrence. For all of the patients in which a second recurrence was not observed, the observed interval was shorter than the DFI until first recurrence. Local recurrence should be considered systemic disease. Many of the patients who underwent resection of the local recurrence experienced a second recurrence after longer observation. We believe that patients with local recurrence should be observed for a period of about double the DFI.     

Long-term prognosis of patients with local recurrence after conservative surgery and radiotherapy for early breast cancer

We have studied the long-term prognosis of 266 patients considered to have isolated local recurrence in the breast following conservative surgery and radiotherapy for early breast cancer. The median follow-up of the patients still alive after diagnosis of local relapse was 11.2 years. At 10 years from the date of salvage treatment, the overall survival rate for the 226 patients with invasive local recurrence was 39% (95% CI, 32-46), the distant recurrence-free survival rate was 36% (95% CI, 29-42), and the local control rate (i.e., survival without subsequent local recurrence or local progression) was 68% (95% CI, 62-75). Among patients with a local recurrence at or near the original tumour site a better distant disease-free survival was observed for patients with recurrences measuring 1cm or less, compared to those with larger recurrences. This suggests, though does not prove, that early detection of local recurrence can improve the treatment outcome but might as well point towards a different biologic behaviour, facilitating early detection.     

Significance of local recurrence after mastectomy for breast cancer.

In a retrospective study 678 patients who underwent (modified) radical mastectomy between 1970 and 1986 were analysed. By comparing the groups of patients who experienced local recurrence, regional recurrence or distant metastasis during follow-up with patients who remained free of disease, we have tried to gain some insight into the significance of local recurrence. By looking at the prognostic factors and the disease-free period there is hardly any difference between the patients with either a local, regional or distant recurrence. Actuarial survival of patients with local recurrence is slightly better than the survival of patients with distant metastasis (P = 0.009). From our results and from the literature we conclude that an isolated local recurrence after mastectomy for breast cancer is, in most cases, a first manifestation of metastatic disease. Probably only a minority of the local recurrences is caused by tumour cells left behind in the operation field.     

Salvage treatment for loco-regional recurrence following breast conservation therapy for early breast cancer

We reviewed the management of 55 cases of loco-regional recurrence after limited surgery and irradiation for breast cancer. Forty-three patients had disease localized to the breast, with axillary involvement in seven. Four had axillary relapse without tumor recurrence in the breast. Eight had breast recurrence extending to involve the chest wall. Mastectomy was used successfully for 41 first recurrences, and seven were controlled by wide excision; 21 of 48 patients also received chemotherapy and/or hormonal manipulation. Diffuse soft-tissue tumor required systemic therapy first, followed by wide excision when possible. Eighty-nine percent of first recurrences were controlled but disease recurred again in eight patients. Overall, 80% of cases were free of loco-regional disease at a median follow-up of 27 months. Reconstructive surgery was valuable for wound closure after wide resections, and for cosmetic procedures. Despite the previous irradiation, surgery complications were acceptable.     

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.     

Risks of second malignancies after breast cancer treatment: Long-term results

Purpose

To estimate the long-term risk of second malignancies after breast cancer treatment in a large homogeneous cohort from a single institution.

Inflammatory local recurrence after breast-conservation therapy for noninflammatory breast cancer

Inflammatory local recurrence after breast-conserving therapy for noninflammatory breast cancer is uncommon and carries a poor prognosis. Over a 5-year period, 7 such cases were treated at the New York-Presbyterian Hospital/Weill-Cornell Medical Center. The characteristics of these 7 patients were compiled and are reviewed along with a discussion of inflammatory recurrence. Tumor size, location, histologic type, grade, stage, margin status, lymphovascular invasion (LVI), estrogen receptor (ER) status, progesterone receptor (PgR) status, adjuvant therapy, and/or radiation therapy at the time of primary treatment and at recurrence were analyzed. The median survival time was 79 months (range, 26-130 months) for patients initially ER-positive, compared with 23 months (range, 0-67 months) for initially ER-negative patients. The median survival for patients without lymph node involvement was 78 months (range, 26-130 months) compared with 41 months (range, 0-79 months) for those with nodal metastases. Survival time in this series of inflammatory local recurrences correlated with the ER status and lymph node involvement of the primary lesion. The optimal management for inflammatory local recurrence is a multimodality approach combining preoperative chemotherapy and surgery.     

Partial breast irradiation as second conservative treatment for local breast cancer recurrence

PURPOSE: Mastectomy is the treatment of reference for local relapse after breast cancer (BC). The aim of this study was to document the feasibility and the results of associating lumpectomy with partial breast irradiation by interstitial brachytherapy (IB) as local treatment for an isolated ipsilateral BC local recurrence (LR). METHODS AND MATERIALS: Between 1975 and 1996 at Marseille and Nice Cancer Institutes, 4026 patients received lumpectomy and radiotherapy (RT) (50-80 Gy) for a localized breast cancer of which 473 presented a LR. Among these patients, 69 (14.6%) received a second lumpectomy followed by IB, which delivered 30 Gy (Nice, n = 24) or 45-50 Gy (Marseille, n = 45) with 3 to 8 (192)Ir wires in 1 or 2 planes on the 85% isodose. RESULTS: Median age at LR was 58.2 years, median follow-up since primary BC was 10 years, and median follow-up after the second conservative treatment was 50.2 months (range, 2-139 months). Immediate tolerance was good in all cases. Grade 2 to 3 long-term complications (LTC) according to IB dose were 0%, 28%, and 32%, respectively, for 30 Gy, 45 to 46 Gy, and 50 Gy (p = 0.01). Grade 2 to 3 LTC according to total dose were 4% and 30%, respectively, for total doses (initial RT plus IB) < or = 100 Gy or >100 Gy (p = 0.008). Logistic regression showed that the only factor associated with Grade 2 to 3 complications was higher IB doses (p = 0.01). We noted 11 second LRs (LR2), 10 distant metastases (DM), and 5 specific deaths. LR2 occurred either in the tumor bed (50.8%) or close to the tumor bed (34.3%) or in another quadrant (14.9%). Kaplan-Meier 5-year freedom from (FF) LR2 (FFLR2), FFDM, and DFS were 77.4%, 86.7%, and 68.9%, respectively. Overall 5-year survival (OS) was 91.8%. Univariate analysis showed the following factors associated with a higher FFLR2: (1) number of wires used for IB (3-4 vs. 5-8 wires, p = 0.006), (2) IB doses (30-45 Gy vs. 46-60 Gy, p = 0.05), (3) number of planes (1 vs. 2, p = 0.05), (4) interval between primary breast cancer and LR (< 36 months vs. > or =36 months, p = 0.06). Multivariate analysis showed two factors associated with better local control: (1) number of wires (5-8 wires, p = 0.013) and (2) interval between primary breast cancer and LR > or =36 months (p = 0.039). The multivariate analysis showed two factors associated with better FFDM: (1) absence of initial axilla involvement (p = 0.019) and (2) relapse in a different location (p = 0.04). These two factors were also associated with a higher OS. CONCLUSION: Our experience showed that second conservative treatments for local relapse were feasible and gave results comparable to standard mastectomy. We recommend delivering IB doses of at least 46 Gy in 2 planes when initial radiotherapy delivered 50 Gy. The study gives enough information to encourage a Phase III trial that compares radical mastectomy to conservative procedures for localized breast cancer recurrences.