Stefano Martella

Locoregional recurrence risk after lipofilling in breast cancer patients

BACKGROUND Lipofilling has been indicated for postmastectomy and postlumpectomy breast reconstruction. The clinical literatures underline its technical efficacy but experimental studies raise important questions about the potential detrimental effect of adipocytes on the stimulation of cancer growth and reappearance. DESIGN We collected 321 consecutive patients operated for a primary breast cancer between 1997 and 2008 who subsequently underwent lipofilling for reconstructive purpose. For each patient, we selected two matched patients with similar characteristics who did not undergo a lipofilling. RESULTS Eighty-nine percent of the tumors were invasive. Median follow-up was 56 months from the primary surgery and 26 months from the lipofilling. Eight and 19 patients had a local event in the lipofilling and control group, respectively, leading to comparable cumulative incidence curves [P = 0.792; Hazard RatioLipovs No lipo = 1.11 (95% confidence interval 0.47-2.64)]. These results were confirmed when patients undergoing quadrantectomy and mastectomy were analyzed separately and when the analysis was limited to invasive tumors. Based on 37 cases, the lipofilling group resulted at higher risk of local events when the analysis was limited to intraepithelial neoplasia. CONCLUSIONS Lipofilling seems to be a safe procedure in breast cancer patients. Longer follow-up and further experiences from oncological series are urgently required to confirm these findings.BACKGROUND Lipofilling has been indicated for postmastectomy and postlumpectomy breast reconstruction. The clinical literatures underline its technical efficacy but experimental studies raise important questions about the potential detrimental effect of adipocytes on the stimulation of cancer growth and reappearance. DESIGN We collected 321 consecutive patients operated for a primary breast cancer between 1997 and 2008 who subsequently underwent lipofilling for reconstructive purpose. For each patient, we selected two matched patients with similar characteristics who did not undergo a lipofilling. RESULTS Eighty-nine percent of the tumors were invasive. Median follow-up was 56 months from the primary surgery and 26 months from the lipofilling. Eight and 19 patients had a local event in the lipofilling and control group, respectively, leading to comparable cumulative incidence curves [P = 0.792; Hazard Ratio(Lipo vs No lipo) = 1.11 (95% confidence interval 0.47-2.64)]. These results were confirmed when patients undergoing quadrantectomy and mastectomy were analyzed separately and when the analysis was limited to invasive tumors. Based on 37 cases, the lipofilling group resulted at higher risk of local events when the analysis was limited to intraepithelial neoplasia. CONCLUSIONS Lipofilling seems to be a safe procedure in breast cancer patients. Longer follow-up and further experiences from oncological series are urgently required to confirm these findings.

Evaluation of fat grafting safety in patients with intra epithelial neoplasia: a matched-cohort study

BACKGROUND Fat grafting is widely carried out in breast cancer patients to improve quality in breast reconstruction. Recently, in vitro and animal studies have questioned the role of adipose tissues in cancer development. DESIGNS Matched-cohort study. We analysed: (i) 59 intraepithelial neoplasia patients who had undergone lipofilling, with no recurrence between primary surgery and lipofilling. (ii) A control group of 118 matched patients (two controls per lipofilling patient) with the corresponding recurrence-free intervals. Both groups were also matched for main cancer criteria. A local event (LE) was the primary end point, with follow-up starting from the baseline. RESULTS Median follow-up was 63 and 66 months from surgery, and 38 and 42 from baseline, for the lipofilling and control groups, respectively; the 5-year cumulative incidence of LE was 18% and 3% (P = 0.02). Ki-67 was the significant factor in univariate survival analysis. A subgroup analysis showed that lipofilling increased the risk of LE in women <50 years, with high grade neoplasia, Ki-67 ≥ 14 or who had undergone quadrantectomy. CONCLUSION Higher risk of LE was observed in intraepithelial neoplasia patients following lipofilling. Although further studies are required to validate our conclusions, patients belonging to this subgroup should be informed of these results and the potential risks.

The nipple-sparing mastectomy: Early results of a feasibility study of a new application of perioperative radiotherapy (ELIOT) in the treatment of breast cancer when mastectomy is indicated

Background Breast cancer surgery has become less and less mutilating, however a mastectomy is required in the case of multicentric, large tumors or recurrences after conservative treatment. The removal of the nipple areola complex during the mastectomy dramatically increases the feeling of mutilation. To reduce this negative psychological impact, in cancers located outside of the central area of the breast, we propose a new type of nipple-sparing mastectomy associated with intraoperative electron beam radiotherapy (ELIOT) delivered on the region of the areola. The nipple-sparing mastectomy is performed leaving 5 mm of glandular tissue behind the nipple areola complex to preserve its blood supply. The reconstruction is immediately performed with a prosthesis or an autologous flap. Patients and Methods Twenty-five patients were included in the study; two of them had a bilateral nipple-sparing mastectomy. Results Pathological examinations demonstrated the presence of 19 infiltrating carcinomas and 8 ductal carcinoma in situ. Two patients had a superficial skin areolar slough followed by spontaneous healing. One necrosis of the areola occurred due to extensive retroareolar dissection. In the early follow-up, the color of the areola was preserved. All patients except one expressed their satisfaction of having kept their areola. Conclusions These preliminary results are encouraging but they require further studies to evaluate the long-term results, the local recurrence rate and the psychological impact.

Complementary Populations of Human Adipose CD34+ Progenitor Cells Promote Growth, Angiogenesis, and Metastasis of Breast Cancer

Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45(-)CD34(+)CD31(+)CD13(-)CCRL2(+) endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+) mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells (but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer.

Oncological safety of autologous fat grafting after breast conservative treatment: A prospective evaluation

Autologous fat graft to the breast is a useful tool to correct defects after breast conservative treatment (BCT). Although this procedure gains popularity, little is known about the interaction between the fat graft and the prior oncological environment. Evidences of safety of this procedure in healthy breast and after post‐mastectomy reconstruction exist. However, there is paucity of data among patients who underwent BCT which are hypothetically under a higher risk of local recurrence (LR). Fifty‐nine patients, with prior BCT, underwent 75 autologous fat graft procedures using the Colemans technique, between October 2005 and July 2008. Follow‐up was made by clinical and radiologic examination at least once, after 6 months of the procedure. Mean age was 50 ± 8.5 years, and mean follow‐up was 34.4 ± 15.3 months. Mean time from oncological surgery to the first fat grafting procedure was 76.6 ± 30.9 months. Most of patients were at initial stage 0 (11.8%), I (33.8%), or IIA (23.7%). Immediate complication was observed in three cases (4%). Only three cases of true LR (4%) associated with the procedure were observed during the follow‐up. Abnormal breast images were present in 20% of the postoperative mammograms, and in 8% of the cases, biopsy was warranted. Autologous fat graft is a safe procedure to correct breast defects after BCT, with low postoperative complications. Although it was not associated with increased risk of LR in the group of patients studied, prospective trials are needed to certify that it does not interfere in patients oncological prognosis.

The perfusion map of the unipedicled TRAM flap to reduce postoperative partial necrosis

The unipedicled transverse rectus abdominis musculocutaneous (TRAM) flap is a well-known technique for breast reconstruction. However, it is clinically difficult to evaluate the blood perfusion of the flap in the operating room. A new technique of blood supply evaluation, employing indocyanine green dye (ICG) fluorescence videoangiography has been performed in 10 cases of unipedicled TRAM flap breast reconstruction. In our series, the ICG measurement was demonstrated to be a safe, quick, and accurate technique of flap perfusion analysis. We confirmed the presence of individual pattern (“perfusion map”) of the flap perfusion, zone II sometimes not being as well perfused as zone III. In this paper, we present our descriptive findings, and the ICG analysis seems to have a predictive value of unipedicled TRAM flap viability.

Nipple-sparing mastectomy—is it worth the risk?

Nipple-sparing mastectomy (NSM) is a surgical protocol designed to reduce the disabling psychological effects of radical or skin-sparing mastectomy. The preservation of the nipple–areola complex produces a more-natural result of the breast reconstruction, but this preservation is suspected of increasing tumor local recurrence. To reduce this risk, different approaches have been proposed: restrict the inclusion criteria and/or add localized radiation therapy. The local recurrence rate in recent series of patients receiving NSM is comparable with the local recurrence rate in modified radical or skin-sparing mastectomies. Today, the quality of the subcutaneous mastectomy technique allows for a more radical glandular removal, especially in the retroareolar area; therefore, local recurrence is observed in 3–6% of patients at 5 years, consistent with traditional mastectomy.

Nipple Sparing Mastectomy: Does Breast Morphological Factor Related to Necrotic Complications?

Background: Nipple sparing mastectomy (NSM) can be performed for prophylactic mastectomy and the treatment of selected breast cancer with oncologic safety. The risk of skin and nipple necrosis is a frequent complication of NSM procedure, and it is usually related to surgical technique. However, the role of the breast morphology should be also investigated. Method: We prospectively performed an analysis of 124 NSM from September 2012 to January 2013 at the European Institute of Oncology, Milan, Italy, focusing on necrotic complications. We analyzed the association between the risks of skin necrosis and the breast morphology of the patients. Results: Among 124 NSM in 113 patients, NSM procedures were associated with necrosis in 22 mastectomies (17.7%) among which included partial necrosis of nipple-areolar complex (NAC) in 15 of 124 NSM (12.1%) and total necrosis in 4 cases (3.5%). The NAC was removed in 5 NSM cases (4%). The volume of breast removed was the only significant factor increasing the risk of skin necrosis. The degree of ptosis was not significantly related to the necrosis risk. Conclusions: Large glandular specimen increases the risk of NAC necrosis. The degree of ptosis and the distance between the sternal notch and the NAC have no significant impact on necrotic complications in NSM. To reduce the necrotic complications in large breast after NSM, reconstruction should better be performed with autologous flap or slow skin expansion using the expander technique.

A pyoderma gangrenosum following breast reconstruction: A rare cause of skin necrosis

risk factors for wound hematomas. Large core devices are unnecessary when smaller gauge needle core biopsy can achieve the diagnosis, at lower cost and morbidity. This case was amenable to 14G core biopsy, which is highly sensitive in most cases, and complications may have been avoided. The lesion type and patient risk factors should be considered and the biopsy procedure tailored to the individual case.

Breast cancer subtype approximations and loco-regional recurrence after immediate breast reconstruction

BACKGROUND A small but significant proportion of patients with breast cancer (BC) will develop loco-regional recurrence (LRR) after immediate breast reconstruction (IBR). The LRR also varies according to breast cancer subtypes and clinicopathological features. METHODS We studied 1742 consecutive BC patients with IBR between 1997 and 2006. According to St Gallen conference consensus 2011, its BC approximations were applied to classify BC into five subtypes: estrogen receptor (ER) and/or progesterone receptor (PgR) positive, HER2 negative, and low Ki67 (<14%) [luminal A]; ER and/or PgR positive, HER2 negative and high Ki67(≥ 14%) [luminal B/HER2 negative]; ER and/or PgR positive, any Ki67 and HER2 positive [luminal B/HER2 positive]; ER negative, PgR negative and HER2 positive [HER2 positive/nonluminal]; and ER negative, PgR negative and HER2 negative [triple negative]. Cumulative incidences of LRR were compared across different subgroups by means of the Gray test. Multivariable Cox regression models were applied. RESULTS Median follow up time was 74 months (range 3-165). The cumulative incidence of LRR was 5.5% (121 events). The 5-year cumulative incidence of LRR was 2.5% for luminal A; 5.0% for luminal B/HER2 negative; 9.8% for luminal B/HER2 positive; 3.8% for HER2 non luminal; and 10.9% for triple negative. On multivariable analysis, tumor size (pT) >2 cm, body mass index (BMI) ≥ 25, triple negative and luminal B/HER2 positive subtypes were associated with increased risk of LRR. CONCLUSION Luminal B/HER2 positive, triple negative subtypes and BMI ≥ 25 are independent prognostic factors for risk of LRR after IBR.