Reasons why COVID-19 survivors should follow dietary World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations: from hyper-inflammation to cardiac dysfunctions.

The World Cancer Research Fund and American Institute for Cancer Research (WCRF/AICR) advise cancer survivors to follow their lifestyle recommendations for cancer prevention.  Recent research indicates that a proper diet could exerts beneficial metabolic and immune effects in humans through the involvement of several, not yet properly known, metabolic pathways. Here, we argue that following WCRF/AICR recommendations could be a strategy to prevent cardiovascular outcomes [fulminant myocarditis, heart failure, venous thromboembolism (VTE)] and acute respiratory distress syndrome (ARDS) in patients during follow-up post COVID-19 infection. We discuss the metabolic effects of a WCRF/AICR based diet, highlighting on the involved cardio-metabolic pathways related on NLRP3 inflammasome-cytokines axis aimed to improve prognosis of COVID-19, especially in patients with cancer.

A phase-III prevention trial of low-dose tamoxifen in postmenopausal hormone replacement therapy users: the HOT study.

BACKGROUND: Postmenopausal hormone replacement therapy (HRT) relieves menopausal symptoms and may decrease mortality in recently postmenopausal women, but increases breast cancer risk. Low-dose tamoxifen has shown retained activity in phase-II studies. METHODS: We conducted a phase-III trial in 1884 recently postmenopausal women on HRT who were randomly assigned to either tamoxifen, 5 mg/day, or placebo for 5 years. The primary end point was breast cancer incidence. RESULTS: After 6.2 ± 1.9 years mean follow-up, there were 24 breast cancers on placebo and 19 on tamoxifen (risk ratio, RR, 0.80; 95% CI 0.44-1.46). Tamoxifen showed favorable trends in luminal-A tumors (RR, 0.32; 95% CI 0.12-0.86), in HRT users <5 years (RR, 0.35; 95% CI 0.15-0.82) and in women completing at least 12 months of treatment (RR, 0.49; 95% CI 0.23-1.02). Serious adverse events did not differ between placebo and tamoxifen, including, respectively, coronary heart syndrome (6 versus 4), cerebrovascular events (2 versus 5), VTE (2 versus 5) and uterine cancers (3 versus 1). Vasomotor symptoms were 50% more frequent on tamoxifen. CONCLUSIONS: The addition of low-dose tamoxifen to HRT did not significantly reduce breast cancer risk and increased climacteric symptoms in recently postmenopausal women. However, we noted beneficial trends in some subgroups which may deserve a larger study.

High Ki67 predicts unfavourable outcomes in early breast cancer patients with a clinically clear axilla who do not receive axillary dissection or axillary radiotherapy.

AIM: Axillary dissection is increasingly forgone in early breast cancer patients with a clinically negative axilla. The GRISO 053 randomised trial recruited 435 patients of age over 45 years, tumour ≤1.4 cm and clinically negative axilla, to assess the importance of axillary radiotherapy versus no axillary radiotherapy in patients not given axillary dissection. In the present study on a subgroup GRISO cases our aim was to assess the prognostic importance of tumour biological factors after more than 10 years of follow-up. METHODS: We retrospectively assessed biological factors in a subgroup of 285 GRISO cases (145 given axillary radiotherapy; 140 not given axillary radiotherapy) with complete biologic, therapeutic and follow-up information, using multivariable Cox proportional hazards regression modelling. RESULTS: Only 10-year cumulative incidence of distant metastasis was lower in the axillary radiotherapy (1%) than no axillary radiotherapy arm (7%) (p=0.037). Irrespective of study arm, hormone receptor positivity had significantly favourable effects on 10-year disease-free survival (DFS) and overall survival. human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes were associated with lower 10-year DFS (60% and 76%, respectively) than luminal A (96%) and B (91%) (p=0.001). Ten-year DFS for high (≥14%) Ki67 cancers was lower than for low Ki67 cancers (p=0.027); however, this effect was mainly confined to the no axillary radiotherapy arm. CONCLUDING STATEMENT: For patients with clinically node-negative small breast cancer not given axillary dissection, 10-year DFS is worsened by HER2 positivity, triple-negative phenotype and high Ki67. Axillary radiotherapy counteracts the negative prognostic effect of high Ki67 in patients not receiving axillary dissection.

Fasting glucose and treatment outcome in breast and colorectal cancer patients treated with targeted agents: results from a historic cohort.

BACKGROUND: We investigated pretreatment fasting glucose as a predictor of patients' important outcomes in breast and colorectal cancers undergoing targeted therapies. PATIENTS AND METHODS: In a historic cohort of 202 breast and 218 colorectal cancers treated with targeted agents from 1998 to 2009, we used the Kaplan-Meier method and the log-rank test to estimate survival through tertiles of fasting glucose and the Cox proportional hazards model for multivariate analysis stratified by primary site of cancer and including gender, age and body mass index. RESULTS: The median follow-up was 20 months (1-128). At 60 months, 65% of patients in the lowest tertile of fasting glucose did not experiment disease progression compared with 34% in the highest tertile (P=0.001). Seventy-six percent of females in the lowest tertile showed no progression compared with 49% in the top tertiles (P=0.015). In multivariate analysis, fasting glucose was a significant predictor of time to disease progression only in breast cancer patients in the first tertile compared with the third (P=0.017). CONCLUSIONS: We found evidence of a predictive role of pretreatment fasting glucose in the development of resistance in breast cancer patients treated with targeted agents. Prospective studies are warranted to confirm our findings.

Preoperative weekly cisplatin, epirubicin, and paclitaxel (PET) improves prognosis in locally advanced breast cancer patients: an update of the Southern Italy Cooperative Oncology Group (SICOG) randomised trial 9908.

BACKGROUND: The present article reports the updated survival outcome of the 200 patients enrolled in the Southern Italy Cooperative Oncology Group 9908 trial, which compared 12 weekly cycles of cisplatin-epirubicin-paclitaxel (PET) with 4 triweekly (once every 3 weeks) cycles of epirubicin-paclitaxel (ET) in patients with locally advanced breast cancer (LABC). METHODS: The effects of treatment, pathologically documented response (pathological response), pre- and post-treatment biomarkers on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) are analysed. RESULTS: At a median follow-up of 74 (range 48-105 months) months, the 5-year RFS, DMFS, and OS were 64 % versus 53% (P = 0.11), 73% versus 55% (P = 0.04), and 82% versus 69% (P = 0.07) in PET and ET, respectively. At multivariate analysis, after adjusting treatment effect for pretreatment biomarkers, PET independently predicted better DMFS (P = 0.018) and OS (P = 0.03), whereas the impact on RFS was of borderline significance (0.057). PET treatment was significantly better than ET treatment only in high-grade or highly proliferating tumours. The better outcome in PET arm was the results of both the higher rate of patients with optimal pathological response and the lower rate of patients with biologically aggressive residual tumour. CONCLUSIONS: The PET weekly regimen significantly improves both DMFS and OS in LABC patients, compared with the triweekly ET combination. The therapeutic advantage is limited to patients with highly aggressive tumours.

Preoperative weekly cisplatin-epirubicin-paclitaxel with G-CSF support in triple-negative large operable breast cancer.

BACKGROUND: Findings from our previously published phase II study showed a high pathologic complete remission (pCR) rate in patients with triple-negative large operable breast cancer after the administration of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles. The safety and efficacy data of the initial population were updated, with inclusion of additional experience with the same therapy. METHODS: Patients with triple-negative large operable breast cancer (T2-T3 N0-1; T > 3 cm) received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel (Taxol) 120 mg/m2, with granulocyte colony-stimulating factor (5 microg/kg days 3-5) support. RESULTS: Overall 74 consecutive patients (T2/T3 = 35/39; N0/N+ = 26/48) were treated, from May 1999 to May 2008. At pathological assessment, 46 women (62%; 95% confidence interval 50-73) showed pCR in both breast and axilla. At a 41-month median follow-up (range 3-119), 13 events (nine distant metastases) had occurred, 5-year projected disease-free survival (DFS) and distant disease-free survival being 76% and 84%, respectively. Five-year DFS was 90% and 56% in pCRs and non-pCRs, respectively. Severe neutropenia and anemia occurred in 23 (31%) and eight (10.8%) patients, respectively. Severe non-hematological toxicity was recorded in <20% of patients. Peripheral neuropathy was quite frequent but never severe. CONCLUSIONS: Eight weekly PET cycles are a highly effective primary treatment in women with triple-negative large operable breast cancer. This approach results in a very promising long-term DFS in this poor prognosis population. This triplet regimen is worthy of evaluation in phase III trials.

Outcome analysis of breast cancer patients receiving breast-conserving surgery in Southern Italy.

The purpose of the current analysis was to evaluate the outcome of patients enrolled at the National Cancer Institute of Naples between 1997 and 2000, who underwent breast-conserving surgery. Between January 1997 and December 2000, 946 patients had been diagnosed with T1 or T2 (<3 cm) breast carcinoma. At the time of the present analysis (31-12-2005), all patients had been followed for >5 years. A Cox proportional hazards model was performed. Overall, 7-year Locoregional Relapse-free survival (LRFS) and Distant Relapse-free Survival (DRFS) rates were 95.9% and 88.4%, respectively. Seven-year DRFS was 91.2% and 79.3% in T1 and T2 stage, respectively (p<0.0001). Multivariate Cox analysis indicated that number of positive lymph-nodes and hormone receptor status were significantly associated with prognosis. Our findings confirm that early diagnosed breast cancer, treated with breast-conserving surgery, is associated with a very good prognosis in patients referred to an Institution which may be considered as representative of similar Cancer Institutes of Southern Italy. The risk of local relapse was found to be very low (4%), although a longer follow-up is needed to draw definitive conclusions.

Weekly cisplatin, epirubicin, and paclitaxel with granulocyte colony-stimulating factor support vs triweekly epirubicin and paclitaxel in locally advanced breast cancer: final analysis of a sicog phase III study.

The present study aimed at evaluating whether a weekly cisplatin, epirubicin, and paclitaxel (PET) regimen could increase the pathological complete response (pCR) rate in comparison with a tri-weekly epirubicin and paclitaxel administration in locally advanced breast cancer (LABC) patients. Patients with stage IIIB disease were randomised to receive either 12 weekly cycles of cisplatin 30 mg m(-2), epirubicin 50 mg m(-2), and paclitaxel 120 mg m(-2) (PET) plus granulocyte-colony stimulating factor support, or four cycles of epirubicin 90 mg m(-2)+paclitaxel 175 mg m(-2) (ET) every 3 weeks. Overall, 200 patients (PET/ET=100/100) were included in this study. A pCR in both breast and axilla occurred in 16 (16%) PET patients and in six (6%) ET patients (P=0.02). The higher activity of PET was evident only in ER negative (27.5 vs 5.4%; P=0.026), and in HER/neu positive (31 vs 5%; P=0.037) tumours. The two arms yielded similar pCR rate in ER positive (PET/ET=7.5/7.1%) and HER/neu negative (PET/ET=10/6%) patients. At a 39 months median follow-up, 70 patients showed a progression or relapses (PET, 32 vs ET, 38). Anaemia, mucositis, peripheral neuropathy, and gastrointestinal toxicity were substantially more frequent in the PET arm. The PET weekly regimen is superior to ET in terms of pCR rate in LABC patients with ER negative and/or HER2 positive tumours Mature data in terms of disease-free and overall survival are needed to ascertain whether this approach could improve the prognosis of these subsets of LABC patients.

Is epirubicin effective in first-line chemotherapy of metastatic breast cancer (MBC) after an epirubicin-containing adjuvant treatment? A single centre phase III trial.

The aim of the study was to demonstrate the superiority of docetaxel and epirubicin vs docetaxel alone as first-line therapy in metastatic breast cancer patients pretreated with adjuvant or neoadjuvant epirubicin. We compared single agent docetaxel 100 mg m-2 (D) with the combination of docetaxel 80 mg m-2 and epirubicin 75 mg m-2 (ED). The response rate (72 vs 79%), the progression-free survival (median 9 vs 11 months) and the overall survival (median 18 vs 21 months) were not significantly different between the ED (n=26) and D arms (n=25), respectively. Leucopaenia, nausea and stomatitis were significantly worse with ED. In conclusion, epirubicin should not be administered in combination with taxanes in metastatic breast cancer patients relapsed after an anthracycline-based adjuvant or neoadjuvant therapy.

A 2-month cisplatin-epirubicin-paclitaxel (PET) weekly combination as primary systemic therapy for large operable breast cancer: a phase II study.

PURPOSE: The present study aimed to define the antitumor activity of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles with granulocyte colony-stimulating factor (G-CSF) support in patients with large operable breast cancer. METHODS: Operable breast cancer (T2-3 N0-1; T >3 cm) patients received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2 and paclitaxel 120 mg/m2, with G-CSF (5 microg/kg, days 3-5) support. RESULTS: Sixty-three patients (T2/T3=30/33; N0/N+=8/55) were enrolled. Thirty-one clinical complete (49%) and 30 partial (48%) responses were recorded, giving a 97% response rate (95% confidence interval 89% to 100%). Breast-sparing surgery was performed in 32/63 (51%) patients. At pathological assessment, 28 patients (45%) showed absence of invasive residual disease in breast and 34 (55%) had negative axilla. In 20 women (32%) both breast and axilla were found to be disease-free. At a 23-month median follow-up (range 4-63), only eight relapses and two deaths had occurred, with the 4-year projected relapse-free and overall survival being 59% and 95%, respectively. Grade 3-4 neutropenia and anemia occurred in 24% and 5% of patients, respectively. Emesis, diarrhea and mucositis were the main non-hematological toxicities; however, only nine (14%) patients experienced one or more episodes of severe non-hematological toxicity. Peripheral neuropathy was frequent, but never severe. CONCLUSIONS: A 2-month weekly treatment with PET represents a well tolerated and highly effective approach in large operable breast cancer patients. In spite of the short duration of chemotherapy, one-third of patients achieved a complete eradication of the tumor in both breast and axilla.

Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy.

BACKGROUND: The need to dissect axillary nodes in patients with early breast cancer and clinically negative axilla remains controversial. The aim of the study was to assess the role of axillary radiotherapy (RT) in reducing axillary metastases in patients with early breast cancer who did not receive axillary dissection. PATIENTS AND METHODS: From 1995 to 1998, 435 patients over 45 years old with breast cancer up to 1.2 cm and no palpable axillary nodes were randomized 214 to breast conservation without axillary treatment and 221 to breast conservation plus axillary RT. RESULTS: After a median follow-up of 63 months, overt axillary metastases were fewer than expected: three cases in the no axillary treatment group (1.5%) and one in the RT group (0.5%). Expected cases were 43 in the no axillary treatment group and 10 in the RT group. Rates of distant metastases and local failures were low, and 5-year disease free survival was 96.0% (95% confidence interval, 94.1%-97.9%) without significant differences between the two arms. CONCLUSIONS: This study suggests that occult axillary metastases might never become clinically overt and axillary dissection might be avoided in patients with small carcinomas and a clinically negative axilla. Axillary RT seems to protect the patients from axillary recurrence almost completely.

Characterization of 2 novel and 2 recurring BRCA1 germline mutations in breast and/or ovarian carcinoma patients from the area of Naples.

We have analyzed 18 families with high incidence of breast cancer or breast and ovarian cancer for the presence of BRCA1 mutations. We identified 4 mutations in the BRCA1 gene in 4 unrelated probands who belong to families with at least 1 case of breast and 1 case of ovarian cancer. Two of the mutations reported in this study are novel (GAA(1172)-->TAA in family Naples 14, GAA(1765)-->TAA in family Naples 20) whereas the others are already present in the Breast Cancer Information Core Electronic Database (http://nchgr.nih.gov/ Intramural research/Lab transfer/Bic/) (5382insC in family Naples 18 and 2080delA in family Naples 19). Conversely, no mutation in the BRCA1 gene was detected in 14 families characterized by 2 or more cases of breast cancer only, even if bilateral and with early-onset. These results indicate that germline mutations in the BRCA1 gene highly predispose for a cancer syndrome that involves the presence of both breast and ovarian cancer.

Radiofrequency ablation in patients with primary breast carcinoma: a pilot study in 26 patients.

BACKGROUND: The authors performed a pilot trial of ultrasound-guided percutaneous radiofrequency ablation (RFA) in patients with T1 and T2 breast tumors 1) to confirm complete coagulative necrosis of tumor tissue and 2) to determine the safety and complications related to this treatment. METHODS: Twenty-six patients with biopsy-proven, invasive breast carcinoma underwent RFA of their breast tumors followed by immediate resection. Treatment was planned to ablate the tumor and a 5 mm margin of surrounding breast tissue. Tumor viability after RFA was assessed by hematoxylin and eosin and nicotinamide adenine dinucleotide vital staining. RESULTS: Twenty patients (77%) had T1 tumors, and six patients (23%) had T2 tumors. The mean greatest dimension of tumors that were treated with RFA was 1.8 cm (range, 0.7-3.0 cm). The mean treatment time for two-phase RFA treatment was 15 minutes and 23 seconds (range, from 6 minutes and 25 seconds to 24 minutes and 54 seconds). Coagulation necrosis of the tumor was complete in 25 of 26 patients (96%): One patient had a microscopic focus of viable tissue adjacent to the needle shaft site. A single patient (1 of 26 patients; 4%) had a complication related to RFA: a full thickness burn of the skin overlying a tumor that was immediately beneath the skin. CONCLUSIONS: This pilot experience with RFA in the treatment of patients with early-stage, primary breast carcinoma revealed that 1) coagulative necrosis of the entire tumor occurred in 96% of the patients, and 2) the treatment was safe, with only a 4% complication rate. The authors have initiated a trial of RFA alone (no resection) for patients with T1 and T2 breast tumors that will include sentinel lymph node mapping and postablation irradiation.

An assessment of delays in obtaining definitive breast cancer treatment in Southern Italy.

Female population is medically underserved in Southern Italy (in comparison with other Italian regions). In a recent systematic review of published studies, delays of 3-6 months between symptom onset and treatment have been clearly associated with lower survival rates for breast cancer patients. The aim of this study was to examine breast cancer delays in medically underserved patients in Southern Italy, in order to recognize their determinating factors so as to provide women with a better opportunity for survival. The variables examined were age, education, symptom status at first presentation: symptomatic and asymptomatic, date of first symptom presentation, date of first consultation with a health provider, consulted provider, tumor size and nodal status, according to the pTNM system. Time intervals were categorized into: < 1 month, 1-3 months and > 3 months for patient and medical delay; 1-3 months, 3-6 months, > 6 months for overall delay. Patient delay was associated with education: a higher risk was found for women with < or = 5 years school attendance (OR = 3.3, 95%, CI 2.0-5.6). Medical delay was seen to be associated with the professional figure: significant differences were found between senologists (oncologist exclusively dedicated to breast cancer) and other specialists (OR 3.5, 95%, CI 1.5-8.4). Age and symptomatic presentation were found to be high risk factors. Concerning tumor size in overall delay in cases > 2 cm had OR values were of 2.4 (95%, CI 1.5-3.7). In conclusion our study suggests that diagnostic delay is associated with medically underserved status and can be reduced by educating younger and less educated women, as suggested in other studies and by providing training programs for members in the medical profession.

Gemcitabine/cyclophosphamide/5-fluorouracil/folinic acid triplet combination in anthracycline- and taxane-refractory breast cancer patients: a Southern Italy Cooperative Oncology Group phase I/II study.

We sought to define the recommended dose of cyclophosphamide (CTX) for subsequent phase II assessment when combined with fixed doses of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and 5-fluorouracil/folinic acid in metastatic breast cancer patients previously treated with anthracyclines and taxanes. Patients age 70 or less, with an Eastern Cooperative Oncology Group performance status 0 to 2, were enrolled. Patients received gemcitabine 1,000 mg/m(2), 5-fluorouracil 425 mg/m(2), folinic acid 100 mg/m(2), and escalating doses of CTX (in 100-mg/m(2) increments), starting at 500 mg/m(2), on days 1 and 8 every 3 weeks. Since March 1999, 46 patients, with a median age of 51 years (range, 38 to 74 years), entered the trial in seven cohorts. Cyclophosphamide dose escalation was stopped at 600 mg/m(2) when three of six patients experienced dose-limiting toxicity (one each with grade 3 thrombocytopenia, grade 3 neutropenia, and persistent grade 2 neutropenia), and then continued with granulocyte colony-stimulating factor support. The CTX dose of 800 mg/m(2) was proven safe and was chosen for phase II study. Two complete and 15 partial responses provided an overall response rate of 37% (95% confidence interval, 23% to 51%). Gemcitabine/CTX/5-fluorouracil/folinic acid is well tolerated by metastatic breast cancer patients pretreated with anthracyclines/taxanes, up to a CTX dose of 800 mg/m(2). The phase II study is ongoing. Semin Oncol 28 (suppl 10):50-56.

Determinant factors for diagnostic delay in operable breast cancer patients.

Randomized trials of mammographic screening have provided strong evidence that early diagnosis and treatment of breast cancer can reduce the specific mortality. Moreover, in a recent systematic review of published studies, delays of 3-6 months between symptom onset and treatment have been clearly found to be associated with lower survival rates for breast cancer patients. The aim of this study was to examine delays registered among breast cancer patients in southern Italy, in order to recognize their determining factors so as to provide women with a better opportunity for survival. The variables examined were age (< 50, 50-64, > or = 65 years), education (< or = 5, > 5 school years); symptom status at first presentation (symptomatic or asymptomatic); date of first symptom presentation; date of first consultation with a health provider; the type of health provider consulted; tumour size and nodal status according to the pTNM system. Time intervals were categorized into: < 1 month, 1-3 months and > 3 months for patient and medical delay; 1-3 months, 3-6 months, > 6 months for overall delay. Patient delay was associated with age and education: a higher risk was found for women of over 65 years age (odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.5) and with < or = 5 years school attendance (OR 3.3, 95% CI 2.0-5.6). Medical delay was seen to be associated with the professional figure: significant differences were found between senologists (oncologists exclusively dedicated to breast cancer operation) and other specialists (OR 3.5, 95% CI 1.5-8.4). Young age and symptomatic presentation were found to be high risk factors. Concerning tumour size in overall delay, in cases where the tumour was > 2 cm the OR was 2.4 (95% CI 1.5-3.7). Our study suggests that diagnostic delay can be reduced by providing more efficient training programmes for members of the medical profession and by producing educational training programmes targeted specifically at each age category (i.e. in older women more attention to education in prevention; in younger women correct information about mammography and specialized structures).

Immediate breast reconstruction with the transverse rectus abdominis musculocutaneous flap after skin-sparing mastectomy.

Immediate breast reconstruction with the transverse rectus abdominis musculocutaneous (TRAM) flap after skin-sparing mastectomy is becoming an increasingly performed procedure in patients with ductal carcinoma in situ, early invasive breast cancer, and prophylactic mastectomy. Through a periareolar approach, it is possible to remove the breast parenchyma along with the nipple areola complex, preserving almost all the original skin envelope and the inframmamary fold. The TRAM flap is used to recreate the volume and shape of the original breast. This technique has higher quality and easier reconstruction. The major disadvantages, extensive scar and donor site skin color mismatch, are reduced to a minimum level because the former is limited at the natural border of the nipple areola and the latter can be effectively concealed with proper nipple reconstruction. Thirty-one patients with a mean age of 39 years (range, 26-50 years) who had undergone unilateral or bilateral mastectomy for early breast cancer and immediate breast reconstruction with the pedicled TRAM flap were retrospectively reviewed. Requirements for the skin-sparing mastectomy technique include suitability of donor site tissue for autologous tissue, early breast cancer or ductal carcinoma in situ, and adequate size and shape matching of the contralateral breast. There was no observed local recur- rence during the follow-up period (mean, 20 months; range, 11-30 months). Complications at the recipient site include mastectomy skin flap partial necrosis in 2 patients and cellulitis of the transferred flap in 1 patient. No total or partial flap necrosis was observed. One patient developed abdominal bulging 1 month after the operation, during the administration of chemotherapy. All reconstruction was considered very satisfactory from an aesthetic perspective by the surgeon and the patient. The nicer aesthetic result with oncological safety is achieved with immediate breast reconstruction with the TRAM flap after skin-sparing mastectomy. The risk of local recurrence is not higher compared with more radical surgical techniques.

Cisplatin-epirubicin-paclitaxel weekly administration with G-CSF support in advanced breast cancer. A Southern Italy Cooperative Oncology Group (SICOG) phase II study.

PURPOSE: It has been shown in vitro that both cisplatin and epirubicin increase the antitumor activity of paclitaxel. Weekly administration could give a substantial improvement in the therapeutic index of cisplatin and paclitaxel. This study was aimed at defining the antitumor activity of a weekly cisplatin-epirubicin-paclitaxel (PET) administration in locally advanced or metastatic breast cancer patients. PATIENTS AND METHODS: Sixty-eight breast cancer patients with advanced disease, who had not received prior chemotherapy (except adjuvant), received weekly cisplatin 30 mg/sqm, paclitaxel 120 mg/sqm and epirubicin 50 mg/sqm plus G-CSF (day 3-5), for a maximum of 12 cycles. Thirty-five patients had stage IIIB and 33 stage IV disease (14 with visceral metastases). RESULTS: All patients were evaluable for response on an intent to treat basis. Overall, 21 complete and 38 partial responses have been recorded for an 87% ORR (95% CI = 76-94%). Fourteen CRs and 19 PRs have been registered in the 35 patients with locally advanced disease for a 94% ORR (95% CI = 81-99%) while 7 CRs and 19 PRs were observed in the 33 patients with metastatic disease for a 79% ORR (95% CI-61-91%). Surgery was performed in 33/35 women with locally advanced disease. Four of these patients (11%) showed no invasive cancer on pathologic examination, and in an additional 8 patients tumor < 1 cm was found in the breast. Only 4/33 patients who underwent surgery relapsed. The projected one-year RFS was greater than 80%. At an 11-month median follow-up (range, 3-19), 11 patients had progressed and 5 had died among the 33 patients with metastatic disease, the median progression-free survival in this group being 14 months. Severe hematologic toxicity was uncommon, grade 3-4 neutropenia and thrombocytopenia occurring in 32% and 4% of patients, respectively. Only 2 episodes of neutropenic sepsis were registered. Packed red blood cell transfusions were required in 7 patients. Vomiting, diarrhoea, mucositis and skin toxicity were severe in 6%, 9%, 10%, and 9% of patients, respectively. Peripheral neuropathy was observed in 47% of patients. CONCLUSIONS: The weekly PET administration is a well tolerated and very effective approach in advanced breast cancer patients. It can produce a 40% clinical complete response rate, with a more than 10% pCR rate in patients with T4 disease, and an about 80% ORR in those with distant metastases. A phase III trial comparing PET with a standard every 3 weeks epirubicin-taxol administration is underway.