Oncological outcome after immediate breast reconstruction for invasive breast cancer: a long-term study.

Immediate breast reconstruction (IBR) was implemented in 1990. Patients operated on for invasive breast cancer were assessed for oncological outcome after a minimum of 5-year follow-up. The study had a form of a retrospective analysis of 203 consecutive patients. The indications for IBR were always discussed in multidisciplinary case conferences. The pectoralis major fascia was left in place. The implant technique dominated. The break down by tumor stage was T1 tumors in 122 cases, T2 in 72, and T3 tumors in nine. Preoperative chemotherapy was given to 21 patients for tumors > 4 cm. Thirteen patients, or 6.5%, developed a local recurrence and seven are still alive with their reconstructed breast after excisions, chemo- and radiation therapy. Most (11) of the 13 recurrences occurred within 24 months after IBR. The recurrence rate remained low with this surgery plus reconstruction approach and IBR is therefore considered a safe procedure when implemented by a multidisciplinary team. Most recurrences appear within 2 years after reconstruction.

Prognostic significance of tumor cell proliferation analyzed in fine needle aspirates from primary breast cancer.

The objective of this study was to analyze the role of proliferating fraction (PF) measured with Ki-67/MIB-1 antibody in a large series of preoperative fine-needle aspirate (FNA) biopsies as a prognosticator of disease recurrence. The study comprised 732 patients who all had a conclusive cytological diagnosis of breast cancer. The follow-up time ranged from 1.2 to 10.2 years with a median of 5.7 years. In multivariate analysis Ki-67/MIB-1 value was a strong (p < 0.001) significant, prognosticator of disease recurrence free interval (DRFI) independent of lymph node status, progesterone receptor content, and tumor size. In the subgroup analysis of 430 node-negative patients the distant recurrence-free rate after 5 years was 94.4% in patients with Ki-67/MIB-1 value < 15% compared to 88.7% in patients with Ki-67/MIB-1 value > or = 15% (p = 0.03). Test of the interaction between tumor size and the value of PF revealed a p-value of 0.06. If the patients, in addition, had a tumor size >20 mm the distant recurrence-free rate after 5 years was 93.2% if Ki-67/MIB-1 < 15% compared to 80.7% in patients with Ki-67/MIB-1 value > or = 15%. This difference was statistically significant (p < 0.01). For patients with tumors <20mm Ki-67/MIB-1 value did not add any prognostic information. In the subgroup of 302 node-positive patients the distant recurrence-free rate after 5 years was 86.0% in patients with Ki-67/MIB-1 value < 15% compared to 70.6% in patients with Ki-67/MIB-1 value > or = 15% (p < 0.01). We conclude that PF assessed by Ki-67/MIB-1 antibodies in preoperative FNA biopsies has a significant prognostic value independent of lymph node status, PgR status and tumor size. To our knowledge, this is the first study demonstrating PF, which can contribute prognostic information when analyzed in preoperative smears.

The role of cathepsin D and PAI-1 in primary invasive breast cancer as prognosticators and predictors of treatment benefit with adjuvant tamoxifen.

In the last few years there has been an increased interest in treatment predictive factors in breast cancer patients. The aim of the study was to analyse the role of cathepsin D and plasminogen activator inhibitor-1 (PAI-1) expression as independent prognosticators and to assess their predictive value with respect to tamoxifen treatment. This study comprises 1851 patients with primary breast cancer diagnosed during 1988-1992. Their median age was 62 years (range: 24-91). The end-point was distant disease recurrence-free interval. Adjuvant treatment with tamoxifen was given to 1136 patients (61%). The median follow-up time was 59 months (range: 39-88). Cathepsin D content was shown to be a significant independent prognosticator in multivariate Cox analysis (P=0.02). The optimal cut-off level was 10 fmol/mg protein, other cut-off levels did not improve the results. The level of cathepsin D also appeared to predict the benefit of tamoxifen among oestrogen receptor (ER)-positive patients although this result did not reach statistical significance (P=0.09). In a multivariate Cox analysis including 497 patients PAI-1 content was shown to be a significant independent prognosticator (P=0.003) but did not appear to predict the benefit of tamoxifen treatment. The optimal cut-off level appeared to be 3 ng/mg protein, which was close to the median value 2.5 ng/mg (range: 0-51). We conclude that cathepsin D is a significant independent prognosticator and may possibly also predict the benefit of tamoxifen amongst ER-positive patients. PAI-1 was also found to be a strong independent prognosticator but no treatment interaction with adjuvant tamoxifen was found.

Proliferating fraction during neoadjuvant chemotherapy of primary breast cancer in relation to objective local response and relapse-free survival.

In women with inoperable primary breast cancer or large T2 tumors, preoperative chemotherapy may induce tumor shrinkage, facilitate surgery and possibly improve survival. However, at present there are no reliable tumor cell parameters to predict which patients will benefit from preoperative chemotherapy. The aims of this study were to analyze the utility of tumor cell proliferation as assessed by Ki-67 staining in fine-needle aspirates from primary breast carcinomas to predict initial response to neoadjuvant chemotherapy as well as recurrence-free survival. The study comprised 51 women with primary breast cancer who received 3-4 courses of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) as neoadjuvant chemotherapy. Tumor cells were procured through fine-needle aspiration biopsy prior to treatment. A second biopsy was performed before the second course of therapy in 33 women. Twenty-nine women (56%) experienced an objective local response after neoadjuvant treatment. During a median follow-up period of 39 months, 21 women (41%) developed disease recurrence. A decrease of more than 25% in proliferating fraction after the first course of chemotherapy correlated significantly with a decreased risk of disease recurrence (p = 0.033) but showed no significant correlation with local objective response. A multivariate analysis revealed that the decrease in proliferating fraction significantly (p < 0.05) added prognostic information to that of involved lymph nodes. These results suggest that changes in proliferating fraction as assessed by Ki-67 staining in fine-needle aspirates during preoperative chemotherapy may be of value in selecting postoperative adjuvant systemic treatment.

Management, morbidity, and oncologic aspects in 100 consecutive patients with immediate breast reconstruction.

BACKGROUND: Immediate breast reconstruction (IBR) is indicated when breast-conserving surgery is inappropriate and the patient refuses mastectomy as the sole procedure. METHODS: Management, morbidity, and oncologic aspects were studied in 100 consecutive patients treated between 1990 and 1994 with a minimum follow-up time of 2 years. Indications for mastectomy and IBR always were discussed within a multidisciplinary group. Eighty-four patients had primary breast cancer, 12 patients underwent salvage mastectomy for an ipsilateral breast tumor recurrence, two patients had benign breast disease, and two patients underwent prophylactic mastectomy because of familial breast cancer. RESULTS: Saline and silicone gel-filled implants were used predominantly (88%), but free and pedicled TRAM flaps were performed in 12 patients (12%). The overall complication rate was 16%. Seven patients lost their implants, three of whom had been irradiated to the chest wall. Sixty-five patients completed breast reconstruction (nipple and areola) within a median time of 418 days (range 40 to 1471 days). At follow-up, eight patients had locoregional recurrences after a median time of 7.2 months (range 1 to 23 months), and nine patients had died from disseminated breast cancer. CONCLUSION: IBR is time-consuming, but it is well tolerated and does not interfere with oncologic adjuvant treatment. IBR can be performed with low morbidity by a dedicated multidisciplinary team.