Mario Rietjens

Comparative Study of Surgical Margins in Oncoplastic Surgery and Quadrantectomy in Breast Cancer

BackgroundOncoplastic surgery for breast cancer is a novel concept that combines a plastic surgical procedure with breast-conserving treatment to improve the final cosmetic results. The aim of this study was to evaluate the oncological safety of oncoplastic procedures by studying the status of the surgical margins of the excised tumor specimen in comparison with standard quadrantectomies.MethodsThirty consecutive breast cancer patients undergoing oncoplastic surgery (group 1) and 30 patients undergoing standard quadrantectomy (group 2) were prospectively studied with regard to the stage of breast cancer, the surgical procedures performed, the volume of breast tissue excised, and the histopathology of the tumor specimen, with specific details on surgical margins.ResultsPatients who underwent oncoplastic surgery (group 1) were younger (mean age, 48.73 years) than patients who had a classic quadrantectomy (group 2; mean age, 55.76 years; P = .022). The mean volume of the excised specimen in group 1 was 200.18 cm3, compared with 117.55 cm3 in group 2 (P = .016). Surgical margins were negative in 25 cases out of 30 in group 1 and 17 out of 30 in group 2 (P = .05). The average length of the surgical margin was 8.5 mm in group 1 and 6.5 mm in group 2, but the difference was not statistically significant (P = .074).ConclusionsOncoplastic surgery adds to the oncological safety of breast-conserving treatment because a larger volume of breast tissue can be excised and a wider negative margin can be obtained. It is especially indicated for large tumors, for which standard breast-conserving treatment has a high probability of leaving positive margins.

The oncologic outcome and immediate surgical complications of lipofilling in breast cancer patients: a multicenter study--Milan-Paris-Lyon experience of 646 lipofilling procedures.

Background: Lipofilling is now performed to improve the breast contour, after both breast-conserving surgery and breast reconstruction. However, injection of fat into a previous tumor site may create a new environment for cancer and adjacent cells. There is also no international agreement regarding lipofilling after breast cancer treatment. Methods: The authors included three institutions specializing in both breast cancer treatment and breast reconstruction (European Institute of Oncology, Milan, Italy; Paris Breast Center, Paris, France; and Leon Berard Centre, Lyon, France) for a multicenter study. A collective chart review of all lipofilling procedures after breast cancer treatment was performed. Results: From 2000 to 2010, the authors reviewed 646 lipofilling procedures from 513 patients. There were 370 mastectomy patients and 143 breast-conserving surgery patients. There were 405 patients (78.9 percent) with invasive carcinoma and 108 (21.1 percent) with carcinoma in situ. The average interval between oncologic surgical interventions and lipofilling was 39.7 months. Average follow-up after lipofilling was 19.2 months. The authors observed a complication rate of 2.8 percent (liponecrosis, 2.0 percent). Twelve radiologic images appeared after lipofilling in 119 breast-conserving surgery cases (10.1 percent). The overall oncologic event rate was 5.6 percent (3.6 percent per year). The locoregional event rate was 2.4 percent (1.5 percent per year). Conclusions: Lipofilling after breast cancer treatment leads to a low complication rate and does not affect radiologic follow-up after breast-conserving surgery. A prospective clinical registry including high-volume multicenter data with a long follow-up is warranted to demonstrate the oncologic safety. Until then, lipofilling should be performed in experienced hands, and a cautious oncologic follow-up protocol is advised. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II. Figure. No caption available.

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.

Can breast reconstruction with gel-filled silicone implants increase the risk of death and second primary cancer in patients treated by mastectomy for breast cancer?

An increased risk of cancer and autoimmune disease associated with gel-filled silicone implants has been suggested recently, but these possible detrimental effects have not been adequately studied in patients with breast cancer. In order to evaluate these effects, we have studied 146 patients with b

Nipple sparing mastectomy: Can we predict the factors predisposing to necrosis?

BACKGROUND Nipple sparing mastectomy (NSM) is an accepted surgical approach in selected breast cancer and prophylactic mastectomy, nevertheless post-mastectomy skin necrosis is one of the frequent complications. This study aimed to analyze the factors that may lead to skin necrosis after NSM. PATIENTS AND METHODS From May 2010 to July 2010, we prospectively registered 50 consecutive NSM from 45 patients. There were 40 mastectomies for cancer, and 10 prophylactic mastectomies. The various patients and surgical factors were registered during pre-, intra- and postoperative period. RESULTS No total necrosis of the nipple areola complex (NAC) was observed. There were thirteen cases with partial necrosis (26.0%) of the areola or the adjacent skin. All these necrosis were partial both for the surface and the thickness. Surgical debridement was performed in 9 (18.0%) cases. The significant risk factors are smoking, young age, type of incision and NAC involvement with areola flap thickness less than 5 mm. CONCLUSION NSM should be done with high caution in smokers. Young patients, periareolar incision and superior circumareolar incision have also a higher risk of necrosis. We recommend keeping areolar flap thickness more than 5 mm in areola region.

Risk factors associated with recurrence after nipple-sparing mastectomy for invasive and intraepithelial neoplasia

BACKGROUND To identify risk factors of recurrence in a large series of patients with breast cancer who underwent a nipple-sparing mastectomy (NSM). PATIENTS AND METHODS Breast-related recurrences and local recurrences (LR) in the breast and the nipple areola complex (NAC) were studied. Cumulative incidences of events were estimated through competing risk analysis. Multivariate Cox regression models were also applied. RESULTS We identified 934 consecutive NSM patients during 2002-2007. Median follow-up was 50 months. In 772 invasive carcinoma patients, the rate of LR in the breast and in the NAC was 3.6% and 0.8%, respectively. In the 162 patients with intraepithelial neoplasia, the rate of LR in the breast and in the NAC was 4.9% and 2.9%, respectively. The significant risk factors of LR in the breast for the group A were grade, overexpression/amplification of HER2/neu and breast cancer molecular subtype Luminal B. In group B, the risk factors of LR in the breast and in the NAC were age (<45 years), absence of estrogen receptors, grade, HER2/neu overexpression and high Ki-67. CONCLUSIONS The LR rate after NSM in our series was low. Biological features of disease and young age should be taken into account when considering NSM in breast cancer patients.BACKGROUND To identify risk factors of recurrence in a large series of patients with breast cancer who underwent a nipple-sparing mastectomy (NSM). PATIENTS AND METHODS Breast-related recurrences and local recurrences (LR) in the breast and the nipple areola complex (NAC) were studied. Cumulative incidences of events were estimated through competing risk analysis. Multivariate Cox regression models were also applied. RESULTS We identified 934 consecutive NSM patients during 2002-2007. Median follow-up was 50 months. In 772 invasive carcinoma patients, the rate of LR in the breast and in the NAC was 3.6% and 0.8%, respectively. In the 162 patients with intraepithelial neoplasia, the rate of LR in the breast and in the NAC was 4.9% and 2.9%, respectively. The significant risk factors of LR in the breast for the group A were grade, overexpression/amplification of HER2/neu and breast cancer molecular subtype Luminal B. In group B, the risk factors of LR in the breast and in the NAC were age (<45 years), absence of estrogen receptors, grade, HER2/neu overexpression and high Ki-67. CONCLUSIONS The LR rate after NSM in our series was low. Biological features of disease and young age should be taken into account when considering NSM in breast cancer patients.

Breast reconstructive techniques in cancer patients: which ones, when to apply, which immediate and long term risks?

Breast reconstruction is considered as part of the breast cancer treatment when a mastectomy is required. The techniques available today, allow reconstruction of the breast even in almost all the cases even in poor local conditions. In 60-70% of the cases, the reconstruction can be performed with an implant inserted behind the pectoralis muscle. Special implants called expanders, are inflatable progressively in the postoperative course thanks to a reservoir located subcutaneously. They provide a progressive distention of the teguments and a more natural shape after substitution of the expander with a definitive implant. The symmetry is usually obtained thanks to a contralateral plastic surgery, which allows at the same time histological check up of the glandular tissue of the opposite breast. The nipple areolar complex is usually reconstructed in a second stage under local anesthesia, using local flaps for the nipple and a tattoo for the colour of the areola. In 30% of the cases, especially after radiotherapy when a salvage mastectomy is required, a flap reconstruction is preferred. The autologous tissue reconstruction with the rectus myocutaneous flap gives excellent cosmetic results and the most natural shape for the breast. But it is a more demanding technique requiring a good experience. In some occasions, the reconstruction with the latissimus flap can also be autologous but usually requires the addition of prosthesis. In most cases, the reconstruction can be performed immediately. The delayed reconstruction is usually preferred when the adjuvant chemotherapy should be delivered as soon as possible after the mastectomy. Complications of the reconstruction such as local necrosis or infections, leading to implant removal or revision of the flap could be detrimental to the patient in delaying the start of the chemotherapy. It is not recommended to reconstruct the breast immediately in case of locally advanced breast cancer. Partial breast reconstruction using plastic surgery procedures can also be performed in case of quadrantectomy in order to obtain a better cosmetic result. Local glandular flaps, as well as specific incisions according to the location of the tumor in the breast allow the reshaping of the breast even in case of large resection and, therefore, provide an opportunity to increase the number of conservative treatment indications, especially in case of in-situ carcinomas.

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.