J.Y. Petit

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.

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.

Immediate breast reconstruction and high-dose chemotherapy.

Background:Immediate breast reconstruction (IBR) is considered as a safe procedure nowadays, and it can be proposed in the majority of patients requiring a mastectomy. In fact, recent studies have demonstrated that immediate breast reconstruction is not detrimental also to patients with locally advanced breast cancers. However, IBR should be reevaluated in case of locally advanced breast cancer requiring high-dose chemotherapy (HDCT). The aim of this study is to evaluate both the risk of chemotherapy delay due to surgical complications and the risk of late surgical complications related to the association with HDCT. We considered 3 series of 23, 67, and 15 patients requiring a mastectomy at the European Institute of Oncology in Milan. After mastectomy, these groups respectively received an IBR and HDCT, an IBR and conventional chemotherapy, and only HDCT with no IBR. Methods:Files of 105 patients who were admitted to our department from October 1999 to January 2002 were reviewed. Twenty-three patients underwent a mastectomy, followed by IBR and HDCT; 67 underwent a mastectomy plus IBR plus conventional CT; and, finally, 15 underwent a mastectomy alone followed by HDCT. The reconstructive techniques performed were 72 permanent prosthesis and 18 temporary expanders. We excluded all patients with IBR by flap (latissimus dorsi or pedicled rectus abdominis) to improve the homogeneity of the sample. Results:All patients who underwent IBR started high-dose chemotherapy without any delay; the time elapsed between surgery and HDCT is not significantly different for patients with and without IBR (54 versus 60 days, P = 0.13). The early complication rate (before CT) was 2.9% (2 patients with infection). The late complication rate (after CT) was higher for the group that underwent IBR followed by HDCT (39% versus 20%). Conclusion:We did not observe any delay for the administration of high-dose chemotherapy after mastectomy with IBR surgery. The complication rate before HDCT is similar to the complication rates published in the literature. On the contrary, we observed a higher rate of infections (13% versus 0%, P = 0,014) after HDCT than after conventional CT, which can be related to the association with high-dose chemotherapy, inducing a decrease of the immune defenses. These results seems to demonstrate that the association of IBR with HDCT is not detrimental to patients from the oncological point of view, but the impact of HDCT on the reconstruction is more negative. Further studies are needed to verify if this risk exists, although lower, in the association with conventional CT. However, a careful evaluation of the risk of infections should be considered preoperatively, and perioperative contaminations should be carefully prevented.

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.

Nipple Sparing Mastectomy: from prophylactic to therapeutic standard.

The indications of Nipple Sparing Mastectomy (NSM) are being broadened, including prophylactic or risk-reduction mastectomy and therapeutic mastectomy for both benign and malignant breast diseases (1-3). Concurrently with the development of better screening protocol and preoperative Magnetic resonance imaging (MRI), now the rate of mastectomy is increasing (4).

Recycling spare tissues: splitting a bipedicled TRAM flap for reconstruction of the contralateral breast

A new method of bipedicled transverse rectus abdominis myocutaneous flap splitting to reconstruct the contralateral breast 1 year after the first breast reconstruction is presented. This technique can be useful in cases of large salvage mastectomy for asynchronous breast cancers allowing a bilateral thoracic closure.

Primary and secondary breast reconstruction with special emphasis on the use of prostheses.

Breast reconstruction (BR) is widely accepted as part of the surgical treatment of breast cancer, although mastectomy is less frequently indicated. Delayed breast reconstruction (DBR) is available for patients having undergone a mastectomy in the past, and immediate breast reconstruction (IBR) can be proposed at the time of mastectomy, especially in case of diffuse or extensive in situ carcinomas. Patients with infiltrating carcinomas who require mastectomy are increasingly treated with adjuvant chemotherapy. Therefore, IBR should be considered as an option only if it does not postpone medical treatment, since delay of adjuvant treatment due to IBR can increase the risk of complications, these being directly related to the IBR technique. An evaluation of the risk should help us to decide whether IBR is safe or not when adjuvant treatment is required.

Cosmetic and reconstructive surgery and risk of breast cancer

SUMMARY Cosmetic surgery of the breast has been performed since the onset of plastic surgery and nowadays it is a part of cancer treatment. In the last decades, cancer risk related to these procedures has been investigated, especially with regards to implant reconstructions. Experimental studies and clinical trials have been published testing different filling materials of prostheses, first in animals and then in human bodies. In no human study has a cancer transformation been induced by filling materials. Moreover, in the case of implant placement no evidence of delayed diagnosis of local recurrence or primary cancer has been described in literature. With regards to autologous tissue reconstructions, they do not add an increased risk of recurrences or secondary cancer. In addition, small areas of liponecrosis and liposclerosis inside the flaps can be easily investigated with ultrasonography and/or with a mammogram. Another cosmetic procedure is frequently proposed to improve final aesthetic results in patients who underwent a breast reconstruction: a reduction mastoplastly or mastopexy of the contralateral breast. This procedure adds a cancer benefit since a pathological examination of the reduction specimens is always performed. With regards to cosmetic breast augmentation, although the silicone prosthesis behind or above the gland decreased the percentage of breast tissue visualized with a mammogram, the ultrasonography allows a good evaluation both of the glandular tissue and the implant. In this paper we evaluate experimental and clinical data in literature concerning cosmetic and reconstructive surgery and risk of breast cancer. We conclude that breast cosmetic surgery should be considered as a safe procedure if performed after a careful ‘carcinogenic’ check-up preoperatively and planned pathological examinations of any specimen.

Abstract 2311: Two complementary populations of human adipose tissue CD34+ progenitors promote breast cancer angiogenesis, growth, and metastases.

We recently reported that human white adipose tissue (WAT) progenitors promote breast cancer growth and metastases in preclinical models (Martin-Padura et al, 2012). Here we report that two populations of human WAT progenitors cooperate in breast cancer angiogenesis, growth and metastatic progression. Sorting, electron microscopy, culture and in vivo studies defined human WAT CD45-CD34+CD31+CD13-CCRL2+ endothelial progenitors (EPCs) as small, undifferentiated cells overexpressing endothelial-restricted genes (VE-Cadherin, Claudin 5; Tie-2, ICAM-2, Dll4, etc) and able to generate in vitro and in vivo mature endothelial cells. A second population of purified WAT CD45-CD34+CD31-CD13+CD140b+ pericyte progenitors (PPCs) was found to overexpress perivascular genes (Endosialin, Adam12, PDGF receptors, TGFbeta, CD44, RUNX1, etc). In vivo and in vitro, CD34+ PPCs generated differentiated CD34- pericytes and adipocytes. In co-culture, WAT EPCs and PPCs - together - induced in ductal breast cancer cell lines an overexpression of EMT genes (SNAIL2, ZEB1, MAP1B, etc). Similarly, WAT EPCs and PPCs induced - together - an increase in breast cancer cell migration towards chemoattractants. When only EPCs or only PPCs were added to breast cancer cell cultures, their EMT- and migration-induction effects were significantly lower than those observed when both EPCs and PPCs were co-cultured together. In vivo, human WAT EPCs and PPCs increased breast cancer angiogenesis, growth and metastases in several orthotopic models. When only EPCs or only PPCs were injected, their effects on breast cancer growth and metastases were significantly reduced in comparison to the effects observed when EPCs and PPCs were injected together. Z-stack showed that functional cancer blood vessels with a lumen were made of human cells only when EPCs and PPCs were co-injected together. To understand WAT EPCs and PPCs migration potential, we measured WAT EPCs and PPCs in the blood of patients before and after different stem cell mobilization procedures. WAT-EPCs (always Citation Format: Stefania Orecchioni, Giuliana Gregato, Ines Martin-Padura, Patrizia Mancuso, Angelica Calleri, Chiara Corsini, Stefano Martella, Jean-Yves Petit, Francesco Bertolini. Two complementary populations of human adipose tissue CD34+ progenitors promote breast cancer angiogenesis, growth, and metastases. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2311. doi:10.1158/1538-7445.AM2013-2311