The safety of breast-conserving surgery in patients who achieve a complete pathologic response after neoadjuvant chemotherapy

BACKGROUND: The objectives of this study were to determine the locoregional recurrence (LRR) rate and to evaluate the correlation between surgical resection volume (RV) and LRR in patients with breast cancer who underwent segmental mastectomy after achieving a pathologic complete response (pCR) on neoadjuvant chemotherapy. METHODS: The authors reviewed the outcomes of all 109 patients who underwent segmental mastectomy after the complete eradication of invasive disease by neoadjuvant chemotherapy at their institution between 1987 and 2002. LRRs were recorded, and RVs after segmental mastectomy were calculated and categorized as small, medium, or large. RESULTS: At a median follow-up of 6.6 years, 3 patients (2.7%) developed LRR. In 2 of those patients, the recurrence was located in the ipsilateral breast; in the other patient, the recurrence was located in the supraclavicular lymph nodes with synchronous distant metastases. The median RV was 73.12 cm3 (range, 2.82-451.51 cm3). Large RVs (>125 cm3) were less common than small RVs (up to 70 cm3) or medium RVs (between 70 cm3 and 125 cm3; P = .009 and P<.0001, respectively). One patient with a small RV had an LRR at 4 years, and 2 patients with medium RVs had LLRs at 2.3 years and 6 years, respectively. The 5-year and 10-year LRR-free survival rates were 98.1% and 96.5%, respectively, and the corresponding overall survival rates were 96% and 92%, respectively. CONCLUSIONS: Segmental mastectomy was associated with excellent locoregional control in patients who achieved a pCR after neoadjuvant chemotherapy. Prospective studies are needed to examine whether decreasing the RVs in this patient population leads to an increased LRR rate.     

Disease-free and overall survival after pathologic complete disease remission of cytologically proven inflammatory breast carcinoma axillary lymph node metastases after primary systemic chemotherapy

BACKGROUND: Breast carcinoma axillary lymph node (ALN) pathologic complete response (pCR) after primary chemotherapy is associated with significantly higher recurrence-free survival (RFS) and overall survival (OS) rates. The purpose of the current study was to determine long-term outcome in patients achieving a pCR of cytologically proven inflammatory breast carcinoma ALN metastases after primary chemotherapy. METHODS: Patients with cytologically documented ALN metastases from inflammatory breast carcinoma were treated in three prospective primary chemotherapy trials. After surgery, patients were subdivided into those patients with and those patients without residual ALN carcinoma. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 175 patients treated, 61 had cytologically confirmed ALN metastases. Fourteen patients (23%) achieved a pCR of the ALNs after primary chemotherapy. The 5-year OS and RFS rates were found to be improved in those patients achieving a pCR of the ALNs (82.5% [95% confidence interval (95% CI), 62.8-100%] and 78.6% [95%CI, 59.8-100%], respectively, vs. 37.1% [95%CI, 25.4-54.2%] and 25.4% [95%CI, 15.5-41.5%], respectively) (P = 0.01 [for OS] and P = 0.001 [for RFS]). Combination anthracycline and taxane-based primary chemotherapy resulted in significantly more patients achieving an ALN pCR (45% vs. 16%; P = 0.01). CONCLUSIONS: pCR of ALN metastases is associated with an excellent prognosis in patients with inflammatory breast carcinoma. The rates of ALN pCR are nearly 50% in patients with inflammatory breast carcinoma who are treated with anthracyclines and weekly paclitaxel before surgery. However, those patients with residual ALN disease at the time of surgery greatly require the introduction of novel therapeutic strategies.     

Randomized trial of high-dose chemotherapy and autologous hematopoietic stem cell support for high-risk primary breast carcinoma: follow-up at 12 years

BACKGROUND: The authors previously reported results from a randomized trial of standard-dose chemotherapy with combined 5-fluorouracil (1000 mg/m2 per cycle), doxorubicin (50 mg/m2 per cycle), and cyclophosphamide (500 mg/m2 per cycle) (FAC) versus FAC followed by high-dose chemotherapy (HDCT) and autologous stem cell support (ASCS) for patients with high-risk primary breast carcinoma. After a median follow-up of 6.5 years, no significant differences were observed in recurrence-free survival (RFS) or overall survival (OS) between the 2 arms. This report updates the survival analyses. METHODS: Patients with >or=10 positive axillary lymph nodes after primary surgery or >or=4 positive lymph nodes at surgery after neoadjuvant chemotherapy were eligible. All patients were to receive 8 cycles of FAC. Patients were assigned randomly to receive either no further chemotherapy or 2 cycles of combined high-dose cyclophosphamide (5250 mg/m2 per cycle), etoposide (1200 mg/m2 per cycle), and cisplatin (165 mg/m2 per cycle) with ASCS. Primary endpoints were RFS and OS. RFS and OS were calculated by using the Kaplan-Meier method. The log-rank statistic was used to compare treatment arms. RESULTS: Between 1990 and 1997, 78 patients were registered, and 39 patients were assigned randomly to each arm. The median follow-up for all patients who were alive at last follow-up was 142.5 months (range, 45-169 months). An intention-to-treat analysis showed no significant difference between the 2 arms in terms of RFS (at 10 years: 40% with FAC vs. 26% with FAC plus HDCT; P=.11) or OS (at 10 years: 47% with FAC vs. 42% with FAC plus HDCT; P=.13). CONCLUSIONS: With a median follow-up of nearly 12 years for patients who remained alive, this trial continued to demonstrate no RFS or OS advantage for patients with high-risk primary breast carcinoma treated with HDCT after standard-dose FAC chemotherapy.     

Multimodal treatment for inflammatory breast cancer

This is a retrospective study of 61 patients with clinically diagnosed breast cancer (IBC) treated with multimodality therapy between September 1977 and September 1985. All patients were scheduled to receive three courses of doxorubicin-based chemotherapy followed by mastectomy, further chemotherapy, and postoperative irradiation. Ten patients (16%) obtained a complete response, defined as either resolution of the clinical signs of inflammatory breast cancer (IBC) (4 patients) or no evidence of tumor in the mastectomy specimen (6 patients). Twenty-seven patients (45%) obtained a partial response, defined as a greater than 50% reduction in the clinical signs of inflammatory breast cancer. No response occurred in 24 patients (39%). Immediate mastectomy was done in 56 patients. Five patients whose disease was not resectable received preoperative irradiation. Nine patients at high risk for locoregional failure received postoperative irradiation immediately after mastectomy and before additional chemotherapy. Postoperative irradiation was given to the chest wall and peripheral lymphatics using standard or accelerated fractionation to a maximum dose of 60 Gy. Forty-six patients completed planned treatment including chemotherapy, surgery, and radiotherapy without failure. The minimum follow-up was 36 months. The 5-year actuarial disease-free survival was 70% for the complete response group, and 35% for the partial response group. All patients with no response failed by 34 months. The actuarial 5-year disease-free survival rate for the entire group was 27%. The 5-year actuarial locoregional control was 89% in the complete response group, 68% in the partial response group, 33% in the no response group, and 58% for all patients. Most failures were on the chest wall within the irradiated volume. Chest wall failures were more frequent in those who did not achieve brisk erythema or moist desquamation after postoperative irradiation. We conclude that multimodal treatment of patients with inflammatory breast cancer results in a low incidence of failure if complete response is obtained following initial chemotherapy. The locoregional control rate and actuarial 5-year disease-free survival for the entire group were not improved when mastectomy was done. Surgery should be done in those patients who respond adequately to chemotherapy, so that late sequelae of high-dose breast irradiation can be eliminated. Higher doses of postoperative irradiation may be required to improve local control in those patients with the poorest response to initial chemotherapy.     

Presence of Visceral Larva Migrans in the Urinary Bladder of a Woman in Khorramabad,Iran

The presence of Visceral Larva Migrans (VLM) in a patient is reported. A 57-year- old woman suffering from right upper abdominal and suprapubic pain referred into a clinic in Khorramabad, Lorestan Province, Iran. A cystoscopy was performed and biopsy was taken. The light microscopic study showed a couple of larvae as well as mononuclear inflammatory cell- infiltration. Because occurrence of VLM is potentially problem in rural areas, it is recommended that an educational program to be initiated to prevent and control VLM infection in both rural and urban people. Clinicians also should consider the clinical features of visceral larva migrans.     

Thrombopoietin, but not erythropoietin, directly stimulates multilineage growth of primitive murine bone marrow progenitor cells in synergy with early acting cytokines: distinct interactions with the ligands for c-kit and FLT3

Thrombopoietin (Tpo), the ligand for c-mpl, has been shown to be the principal regulator of megakaryocytopoiesis and platelet production. The ability of Tpo to potently stimulate the growth of committed megakaryocyte (Mk) progenitor cells has been studied in detail. Murine fetal liver cells, highly enriched in primitive progenitors, have been shown to express c-mpl, but little is known about the ability of Tpo to stimulate the growth and differentiation of primitive multipotent bone marrow (BM) progenitor cells. Here, we show that Tpo alone and in combination with early acting cytokines can stimulate the growth and multilineage differentiation of Lin- Sca-1+ BM progenitor cells. In particular, Tpo potently synergized with the ligands for c-kit (stem cell factor [SCF]) and flt3 (FL) to stimulate an increase in the number and size of clones formed from Lin- Sca-1+ progenitors. When cells were plated at 1 cell per well, the synergistic effect of Tpo was observed both in fetal calf serum-supplemented and serum-depleted medium and was decreased if the addition of Tpo to cultures was delayed for as little as 24 hours, suggesting that Tpo is acting directly on the primitive progenitors. Tpo added to SCF + erythropoietin (Epo)-supplemented methylcellulose cultures potently enhanced the formation of multilineage colonies containing granulocytes, macrophages, erythrocytes, and Mks. SCF potently enhanced Tpo-stimulated production of high-ploidy Mks from Lin- Sca-1+ progenitors, whereas the increased growth response obtained when combining Tpo with FL did not translate into increased Mk production. The ability of Tpo and SCF to synergistically enhance the growth of Lin- Sca-1+ progenitors was predominantly observed in the more primitive rhodamine 123(lo) fraction. Tpo also enhanced growth of Lin- Sca-1+ progenitors when combined with interleukin-3 (IL-3) and IL-11 but not with IL-12, granulocyte colony-stimulating factor, granulocyte-macrophage colony- stimulating factor, or Epo. Epo, which has high homology to Tpo, was unable to stimulate the growth of Lin- Sca-1+ progenitors alone or in combination with SCF or FL, suggesting that c-mpl is expressed on more primitive stages of progenitors than the Epo receptor. Thus, the present studies show the potent ability of Tpo to enhance the growth of primitive multipotent murine BM progenitors in combination with multiple early acting cytokines and documents its unique ability to synergize with SCF to enhance Mk production from such progenitors.