Background: The local recurrence (LR) rate with skin-sparing mastectomy (SSM) and immediate breast reconstruction (IBR) has been reported as comparable to the LR rate after conventional mastectomy. However, limited data are available on the prognostic significance and management of LR following SSM. 
Methods: A prospective database maintained at the University of Texas M. D. Anderson Cancer Center identified 437 SSMs performed for 372 invasive T1/T2 breast cancers between 1986 and 1993. 
Results: Twenty-three LRs were identified, with a LR rate of 6.2% (23/372). Twenty-two of these (96%) presented as palpable skin-flap masses. The median time to recurrence was 25 months (range, 3 to 98 months). Fourteen patients were treated with a combination of surgery and systemic therapy. Resection of the reconstructed breast was performed in only three patients. Complete local control of the recurrent disease was achieved in 17 patients (74%). Nine patients (39%) developed distant metastatic disease. At a median follow-up of 26 months, 14 of 23 patients (61%) are alive without evidence of disease, and 7 (30%) have died from breast cancer. 
Conclusions: Because LR rate with SSM is low and likelihood of local control and survival is high, SSM and IBR is an acceptable treatment option for early stage breast cancer.

Presentation, treatment, and outcome of local recurrence after skin-sparing mastectomy and immediate breast reconstruction

Between 1967 and 1988 128 patients with isolated local-regional recurrence of breast cancer after mastectomy were treated with definitive radiation therapy. Recurrence was confined to a single site in 108 patients and multiple sites in 20. The chest wall was the most common location (86) and the supraclavicular region was the second most common (20). Surgical treatment for recurrence prior to irradiation consisted of excision of all gross disease in 78 patients and incisional biopsy in 49 patients. Irradiation was directed to the entire chest wall in 19% of patients with isolated chest wall recurrences and to the chest wall and regional nodes in 81%. In patients with isolated nodal failures, treatment was directed to the nodal site and chest wall in 87% and to the regional site alone in 13%. Patients with multiple sites received treatment to the chest wall and regional nodes in all cases. Electively treated sites usually received 4500–5000 cGy. Following excision of chest wall disease, the median dose was 6000 cGy. Gross disease on the chest wall received a median dose of 6100 cGy. Gross disease in nodal sites received a median dose of 5600 cGy; 66 patients received systemic therapy at recurrence. The 5-year actuarial local-regional control was 43%. In a multivariate analysis only the estrogen receptor status of the recurrence remained significant ( p = .002). The 5-year actuarial survival was 49% with a relapse-free survival of 24%. In a multivariate analysis for survival, the disease-free interval (p = .007 local regional control ( p = .006), and excisional biopsy for recurrence ( p = .03) remained significant. In a multivariate analysis for relapse-free survival, the disease-free interval ( p = .03), excisional biopsy ( p = .0001 and the extent of axillary nodal involvement ( p = .007) remained significant. In the subgroup of patients with a disease-free interval ≥ 24 months, excisional biopsy, and local regional control, the 5-year survival was 61% with a relapse-free survival of 59%. This subgroup represents 18% of the entire group and has a relatively good prognosis after recurrence.

The results of radiation therapy for isolated local regional recurrence after mastectomy.

The role of radiotherapy in the treatment of isolated local recurrence of breast cancer after mastectomy is controversial. In an attempt to define this role, the results of moderate-dose radiotherapy in 90 such patients were reviewed. The median follow-up time for these patients was 81 months. The actuarial probability of local control after treatment was 42% at 5 years and 35% at 10 years. Freedom from distant failure was 30% at 5 years and only 7% at 10 years. The rate of appearance of distant metastasis was fairly constant at approximately 20% of patients per year. Overall survival was 50% at 5 years and 26% at 10 years. Overall survival and relapse-free survival were both chiefly influenced by the disease-free interval (DFI). Patients who presented with a DFI of greater than or equal to 2 years had a 5-year actuarial overall survival rate of 58% compared to 33% for patients with a DFI of less than 2 years (P = 0.04). Subsequent local failures after radiotherapy were principally seen at the initial site of recurrence, but also at other sites in or at the edge of the radiation fields. These results strongly suggest that patients with apparently isolated local recurrence after mastectomy are incurable by further local treatment. Effective systemic therapy is required to improve the results in these patients. Radiotherapy is a useful palliative procedure in patients with long disease-free intervals. The role of radiotherapy in conjunction with systemic therapy is, as yet, undefined.

The use of radiotherapy for treatment of isolated locoregional recurrence of breast carcinoma after mastectomy.

PURPOSE: To study prognostic factors after high-dose chemotherapy (HDC) for patients with stage IV oligometastatic breast cancer. PATIENTS AND METHODS: Sixty patients with minimal metastatic disease amenable to local therapy enrolled onto a prospective HDC trial were analyzed for potential prognostic factors. Tumor blocks were retrospectively collected from referring institutions. RESULTS: Median follow-up was 62 months (range, 4 to 120 months). Median relapse-free survival (RFS) and overall survival (OS) times were 52 and 80 months, respectively. Five-year RFS and OS rates were 52% (95% confidence interval [CI], 39% to 64%) and 62% (95% CI, 49% to 74%), respectively. HER-2 expression, number of tumor sites, primary axillary nodal ratio (number of positive nodes divided by number of sampled nodes), number of positive axillary nodes, and delivery or omission of radiotherapy to metastases correlated with RFS. HER-2 overexpression and more than one site were independent adverse risk factors for RFS. HER-2 an...

Prognostic Model for Relapse After High-Dose Chemotherapy With Autologous Stem-Cell Transplantation for Stage IV Oligometastatic Breast Cancer

Angiogenesis, the formation of new blood vessels from an existing vasculature, is requisite for tumor growth. It entails intercellular coordination of endothelial and tumor cells through angiogenic growth factor signaling. Interruption of these events has implications in the suppression of tumor growth. PD166285, a broad-spectrum receptor tyrosine kinase (RTK) inhibitor, and PD173074, a selective FGFR1TK inhibitor, were evaluated for their anti-angiogenic activity and anti-tumor efficacy in combination with photodynamic therapy (PDT). To evaluate the anti-angiogenic and anti-tumor activities of these compounds, RTK assays, in vitro tumor cell growth and microcapillary formation assays, in vivo murine angiogenesis and anti-tumor efficacy studies utilizing RTK inhibitors in combination with photodynamic therapy were performed. PD166285 inhibited PDGFR-beta-, EGFR-, and FGFR1TKs and c-src TK by 50% (IC50) at concentrations between 7-85 nM. PD173074 displayed selective inhibitory activity towards FGFR1TK at 26 nM. PD173074 demonstrated (>100 fold) selective growth inhibitory action towards human umbilical vein endothelial cells compared with a panel of tumor cell lines. Both PD166285 and PD173074 (at 10 nM) inhibited the formation of microcapillaries on Matrigel-coated plastic. In vivo anti-angiogenesis studies in mice revealed that oral administration (p.o.) of either PD166285 (1-25 mg/kg) or PD173074 (25-100 mg/kg) generated dose dependent inhibition of angiogenesis. Against a murine mammary 16c tumor, significantly prolonged tumor regressions were achieved with daily p.o. doses of PD166285 (5-10 mg/kg) or PD173074 (30-60 mg/kg) following PDT compared with PDT alone (p<0.001). Many long-term survivors were also noted in combination treatment groups. PD166285 and PD173074 displayed potent anti-angiogenic and anti-tumor activity and prolonged the duration of anti-tumor response to PDT. Interference in membrane signal transduction by inhibitors of specific RTKs (e.g. FGFR1TK) should result in new chemotherapeutic agents having the ability to limit tumor angiogenesis and regrowth following cytoreductive treatments such as PDT.

Anti-angiogenic activity of selected receptor tyrosine kinase inhibitors, PD166285 and PD173074: implications for combination treatment with photodynamic therapy.

Local or regional recurrence after primary surgical management for carcinoma of the breast was retrospectively evaluated by presenting stage and management in 121 patients. None had evidence of systemic disease. Management consisted of surgical removal only in 11 patients, removal followed by irradiation in 25, biopsy only followed by irradiation in 43, hormonal therapy after biopsy in 30, and chemotherapy after biopsy in 12. Mean and median follow-up for all patients was 46.9 and 31.5 months, respectively. Patients experiencing a recurrence within 24 months of primary surgical management experienced the worst overall and disease-free survival. The group of 42 patients with residual disease who received systemic therapy after biopsy had improved disease-free and overall survival at 5 years in comparison to the group of 43 patients who received local therapy after biopsy (p less than or equal to 0.05). Radiation therapy produced more frequent and durable control of local disease than did systemic therapy. ...

Local or regionally recurrent carcinoma of the breast: results of therapy in 121 patients.

Photosensitivity reaction following DTIC administration: report of two cases.

Fifty-three patients with advanced metastatic colorectal carcinoma were treated every 4-5 weeks with a chemotherapeutic regimen consisting of 5-FU (300 mg/m2 iv on Days 1-5), mitomycin (10 mg/m2 iv on Day 1 only [repeated every other course]), vincristine (0.75 mg/m2 on Days 1 and 5), and methotrexate (8.0 mg/m2 iv on Days 1 and 5). The overall response rate was 43.4%, with three patients (5.7%) achieving complete response (mean duration, 13.3 months) and 20 patients (37.7%) achieving partial response (mean duration, 6.3 months). Stable disease was not considered to be a response category in this report. The mean overall response duration was 7.8 months. The observed mean survival duration in responders was 15.2 months and in nonresponders was 8.9 months (P less than or equal to 0.01). Hematologic and subjective toxic effects are discussed.

Treatment of metastatic colorectal carcinoma with 5-FU, mitomycin, vincristine, and methotrexate.

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Local or regionally recurrent carcinoma of the breast: results of therapy in 121 patients.

Photosensitivity reaction following DTIC administration: report of two cases.

Treatment of metastatic colorectal carcinoma with 5-FU, mitomycin, vincristine, and methotrexate.