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Biomedical subjects

Marco Greco

Publications and source records attributed to Marco Greco.

8 recordsLinked to original sources
PubMed2006

Allometric scaling law questions the traditional mechanical model for axillary lymph node involvement in breast cancer.

PURPOSE: To find a quantitative relationship between tumor size and frequency of axillary lymph node involvement. PATIENTS AND METHODS: The frequency of axillary node involvement versus primary tumor volume was analyzed in 10 selected series of patients incorporating a total of 57,244 women with resectable breast cancer. The average number of events per unit volume resulting in tumor spread to axillary lymph nodes before tumor surgical removal Theta(V)/V, was estimated under simple probabilistic assumptions. RESULTS: The allometric scaling law Theta(V)/V = 0.0586V(-0.7457) was estimated on the data, fitting the proportion of lymph node involvement on tumor volume V (in microliters). The estimate 0.7457 (95% CI, 0.7200 to 0.7713) suggests that the true scaling exponent, under the assumed model, may be the fractional value, which characterizes scaling relationships for a wide variety of biologic variables at both the whole organism level and organ level. CONCLUSION: Results suggest that the phenomenon should be related to some internal structural trait of the tumor. The vascular network seems to be the best candidate. This result does not support a mere mechanical model of lymphatic tumor spread. A more complex biology-based model of lymphohematogenous spread is suggested, in which the axillary nodes draining the lymph from the primary tumor may become activated by factors produced by both tumor cells and tumor stroma, thus favoring cell-selective homing of otherwise circulating tumor cells. The success of fractal features related to the internal architecture brings additional support to the consideration of primary breast cancer as an organ-like structure.

Axilla↗
PubMed2006

The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal carcinoma in situ (DCIS)?

Lobular carcinoma in situ was first described over 60 years ago. Despite the long history, it continues to pose significant difficulties in screening, diagnosis, management and treatment. This is partly due its multi-focal and bilateral presentation, an incomplete understanding of its biology and natural history and perpetuation of misconceptions gathered over the last decades. In this review, the working group on behalf of EUSOMA has attempted to summarise the current thinking and management of this interesting lesion.

Adult↗
PubMed2006

Skin-reducing mastectomy.

BACKGROUND: The authors propose a combined flap technique to reconstruct large and medium-sized ptotic breasts in a single-stage operation by use of anatomical permanent implants. METHODS: The authors enrolled 28 patients fulfilling criteria for skin-sparing mastectomy and presenting with ptotic breasts whose areola-to-inframammary fold distance was more than 8 cm. All reconstructions were performed as a single-stage procedure. After preoperative planning, a large area in the lower half of the breast was deepithelialized according to the conventional Wise pattern. Mastectomy was then carried out. To perform reconstructions, the inferomedial fibers of the pectoralis major muscle were dissected and sutured to the superior border of the inferior dermal flap. An anatomical implant was then inserted into the pouch, which was closed laterally with the previously harvested serratus anterior fascia. Skin flaps were finally closed down to the inframammary fold. RESULTS: The authors performed 30 procedures on 28 patients. The medium size anatomical implants was 433 cc. Twelve women achieved symmetrization in a single stage ending in a symmetric inverted-T scar. The overall complication rate was 20 percent, with four cases (13 percent) complicated by severe, extensive necrosis of the skin flaps requiring implant removal. CONCLUSIONS: Breast cancer treatment must nowadays optimize cosmetic results. This can be accomplished in selected cases by means of a single-stage operation that the authors call "skin-reducing mastectomy." The final scars imitate those of cosmetic surgery. Careful patient selection and improvement in the learning curve may reduce the complication rate.

Abscess↗
PubMed2005

Feasibility and tolerability of sequential doxorubicin/paclitaxel followed by cyclophosphamide, methotrexate, and fluorouracil and its effects on tumor response as preoperative therapy.

PURPOSE: The European Cooperative Trial in Operable breast cancer (ECTO) randomly tested whether efficacy of adjuvant doxorubicin followed by i.v. cyclophosphamide, methotrexate, and fluorouracil (CMF; doxorubicin-->CMF, arm A) could be improved by adding paclitaxel (doxorubicin/paclitaxel-->CMF) as adjuvant (arm B) or primary systemic therapy (PST, arm C). We report here feasibility, tolerability, locoregional antitumor activity, and breast conservation rate. METHODS: A total of 1,355 women entered the study. Feasibility and safety were compared in arm A versus arms B plus C. Surgical findings were compared in arms A plus B versus arm C. RESULTS: Grade 3 or 4 National Cancer Institute toxicities were low (<5%) in all arms. Neuropathy was more frequent in the paclitaxel-containing arms (grade 2, 20.5% versus 5.0%; grade 3, 1.3% versus 0.2%). At 31 months of follow-up, asymptomatic drop of left ventricular ejection fraction was similar in all arms, whereas symptomatic cardiotoxicity was recorded in three patients (0.5%) in A and in three patients (0.3%) in B plus C. PST induced clinical complete plus partial remission in 78%, with an in-breast pathologic complete response rate of 23% and an in-breast plus axilla pathologic complete response rate of 20%. In the multivariate analysis, only estrogen receptor (ER) status was significantly associated with pathologic complete response (odds ratio for ER negative, 5.77; 95% confidence interval, 3.49-9.52; P<0.0001). PTS induced a significant axillary downstaging (P<0.001), and breast sparing surgery was feasible in 65% versus 34% (P<0.001). CONCLUSIONS: Doxorubicin/paclitaxel-->CMF is feasible, safe, and well tolerated. Given as PST, it is markedly active, allowing for breast-sparing surgery in a large fraction of patients.

Aged↗
PubMed2004

Prospective evaluation of estrogen receptor-beta in predicting response to neoadjuvant antiestrogen therapy in elderly breast cancer patients.

It has been proposed that knowledge of estrogen receptor beta (ER-beta) expression may refine estrogen receptor alpha (ER-alpha) predictivity of response to endocrine therapy. We challenged this hypothesis in ER-alpha-positive breast cancers subjected to preoperative antiestrogen treatment. Forty-seven elderly (> or =65 years old) women with nonmetastatic, ER-alpha-positive (by immunohistochemistry) primary breast cancers (> 2 cm in diameter) entered a neoadjuvant hormone therapy protocol (60 mg/day toremifene for 3 months). ER-alpha and ER-beta (ERs) mRNA was determined by semiquantitative RT-PCR, before (on core needle biopsy) and after (on surgical specimens) neoadjuvant treatment. Study end points included: (1) relation between treatment response and ER mRNA expression; and (2) changes in ER expression after treatment. The response was clinically assessed as tumor size change at the end of the preoperative treatment. ER mRNA expression was assessable before and after treatment in 38 and 20 cases respectively. ER-beta was co-expressed with ER-alpha at variable levels and significantly correlated only with progesterone receptor (P = 0.0285). Objective clinical response, including patients with minor change (> or =25-<50% tumor shrinkage after treatment), was documented in 68.4% of cases and was independent of ER-beta levels or changes. ER-alpha levels were higher in tumors from patients in complete remission than in those from women achieving partial response or minor change compared with non-responsive patients (median expression values: 801 versus 516 versus 320 arbitrary units) and were consistently down-regulated by preoperative treatment. We conclude that in this elderly patient population with ER-alpha-positive tumors, ER-beta mRNA was neither predictive of response to preoperative toremifene nor provided additional information to the knowledge of ER-alpha mRNA levels, which, conversely, were directly correlated with likelihood of response.

Aged↗
PubMed2003

Role of HER2 in wound-induced breast carcinoma proliferation.

OBJECTIVE: Clinical and experimental data have suggested that surgical removal of primary tumours promotes the growth of metastatic lesions. We assessed the effect of surgery on proliferation of breast carcinomas, in particular those overexpressing HER2 oncoprotein. METHODS: Proliferation of breast carcinoma cells was assessed by MIB-1 immunohistochemistry in sections of primary breast carcinomas and in residual tumour found in re-excision specimens, and in in-vitro cell lines by colorimetric assay. Epidermal growth factor (EGF)-like growth factors were measured by displacement of radiolabelled EGF from its receptor. Cellular damage was measured in terms of creatine phosphokinase level. Downmodulation of HER2 was investigated by cytoplasmic expression of anti-HER2 antibody and by inhibition with anti-HER2 antibody trastuzumab. FINDINGS: Residual breast carcinomas that had been surgically removed within 48 days after first surgery showed a significant increase in proliferation if they were HER2-positive. Wound drainage fluid and postsurgical serum samples from patients stimulated in-vitro growth of HER2-overexpressing breast carcinoma cells. Removal of HER2 from the cell membrane led to a striking reduction of the induced proliferation. The amount of EGF-like growth factors in post-surgical serum samples, as well as the extent of drainage-fluid-induced proliferation, directly correlated with the amount of surgical damage assessed by creatine phosphokinase levels (r=0.77, p=0.002 and r=0.69, p=0.009, respectively). Treatment of HER2-positive tumour cells with trastuzumab before adding the growth stimulus abolished drainage-fluid-induced proliferation. INTERPRETATION: HER2 overexpression by breast carcinoma cells has a role in postsurgery stimulation of growth of breast carcinoma cells.

Antibodies, Monoclonal↗
PubMed2002

Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer.

BACKGROUND: We conducted 20 years of follow-up of women enrolled in a randomized trial to compare the efficacy of radical (Halsted) mastectomy with that of breast-conserving surgery. METHODS: From 1973 to 1980, 701 women with breast cancers measuring no more than 2 cm in diameter were randomly assigned to undergo radical mastectomy (349 patients) or breast-conserving surgery (quadrantectomy) followed by radiotherapy to the ipsilateral mammary tissue (352 patients). After 1976, patients in both groups who had positive axillary nodes also received adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil. RESULTS: Thirty women in the group that underwent breast-conserving therapy had a recurrence of tumor in the same breast, whereas eight women in the radical-mastectomy group had local recurrences (P<0.001). The crude cumulative incidence of these events was 8.8 percent and 2.3 percent, respectively, after 20 years. In contrast, there was no significant difference between the two groups in the rates of contralateral-breast carcinomas, distant metastases, or second primary cancers. After a median follow-up of 20 years, the rate of death from all causes was 41.7 percent in the group that underwent breast-conserving surgery and 41.2 percent in the radical-mastectomy group (P=1.0). The respective rates of death from breast cancer were 26.1 percent and 24.3 percent (P=0.8). CONCLUSIONS: The long-term survival rate among women who undergo breast-conserving surgery is the same as that among women who undergo radical mastectomy. Breast-conserving surgery is therefore the treatment of choice for women with relatively small breast cancers.

Antineoplastic Combined Chemotherapy Protocols↗