Alba Di Leone

Oncoplastic techniques in the conservative surgical treatment of breast cancer: an overview.

Abstract:  Conservative surgery has become a well‐established alternative to mastectomy in the treatment of breast cancer. However, in case of larger lesions or small‐size breasts, the removal of adequate volumes of breast tissue to achieve tumor‐free margins and reduce the risk of local relapse may compromise the cosmetic outcome, causing unpleasant results. In order to address this issue, new surgical techniques, so‐called oncoplastic techniques, have been introduced in recent years to optimize the efficacy of conservative surgery both in terms of local control and cosmetic results. This article discusses the indications, advantages, and limitations of these techniques and their results in terms of local recurrence and overall survival. 

Oxidized regenerated cellulose in breast surgery: experimental model

BACKGROUND Breast-conserving surgery (BCS) combined with postoperative radiotherapy has become the gold standard of locoregional treatment in patients with early-stage breast cancer. When large tumor resections are needed in small medium size breasts, oncoplastic procedures (OPP) have been introduced to improve the cosmetic result; but in several cases, OPP may be not sufficient to accomplish this purpose. Oxidized regenerated cellulose (ORC, Tabotamp fibrillar; Johnson & Johnson; Ethicon) has been reported to be useful in OPP to optimize the cosmetic results after OPP. However, no ultrastructural study is available on the use of ORC as a filler in BCS. MATERIALS AND METHODS A BCS cavity was simulated in both groin regions in 24 consecutive Wistar rats. The right groin underwent soft tissue displacement and ORC implantation, whereas the left groin was treated only by soft tissue displacement (control side). Rats were sacrificed at 10, 20, and 30 wk to evaluate volume retainment and microscopic features (vascularization, fibrosis, cell population, inflammation, liponecrosis, and capsule formation). RESULTS The use of ORC was characterized by diffuse fibrosis and homogeneous neovascularization within the construct, with no capsule formation and no inflammation. Volume retainment was similar in the 20- and 30-wk specimens (mean 80.4%, standard deviation, 6.65 and mean 79.9%, standard deviation, 6.51). CONCLUSIONS Implanted ORC was well integrated within the soft tissue with diffuse fibrosis, angiogenesis, and absence of capsule formation. Preliminary results confirmed that this biomaterial could further contribute to optimize cosmetic results in the oncoplastic surgical spectrum of breast-conservation therapy.

Early onset lactating adenoma and the role of breast MRI: a case report

IntroductionLactating adenoma is a benign condition, representing the most prevalent breast lesion in pregnant women and during puerperium; in this paper, a case of a woman with lactating adenoma occurring during the first trimester of pregnancy is reported. There have been no reports in the literature, according to our search, focusing on magnetic resonance imaging findings in cases of lactating adenomas. Also the early onset of the lesion during the first trimester of pregnancy is quite unusual and possibly unique.Case presentationWe report the case of a primiparous 30-year-old Caucasian woman, who noted an asymptomatic lump within her left breast during the 9th week of gestation, slightly increasing in size over the next few weeks. Ultrasound demonstrated a hypoecoic solid mass, hypervascularized and measuring 4 cm. On magnetic resonance imaging, performed in the first month after delivery, the lesion appeared as an ovoidal homogeneous mass, with regular margins and a significant contrast enhancement indicative of a giant adenoma.ConclusionMagnetic resonance imaging could play an important role in the differential diagnosis of pregnancy-related breast lumps, particularly during puerperium, thus avoiding unnecessary surgical biopsies.

Breast MRI in a Case of “Early Onset” Lactating Adenoma

lesion. Biopsy of that lesion showed sheets of plasma cells including immature and binucleated forms, consistent with the diagnosis of plasmacytoma with no evidence of carcinoma. Serum protein electrophoresis revealed a sharp band in the near gamma region (M protein) consistent with IgA kappa paraproteinaemia (Fig. 3), while no Bence Johns proteins were detected in her urine. Skeletal survey revealed a single rounded lytic lesion at the left parietal convexity (Fig. 4). Her bone marrow sample detected the presence of plasmacytoma (Fig. 5) with increased number of plasma cells of 18% (normal < 1.2%). Collectively, all supported the diagnosis of multiple myeloma. Ultrasound guided liver biopsy confirmed the diagnosis of metastatic carcinoma from the breast. The patient’s treatment plan consisted of seven cycles of FEC. Her clinical and radiological evaluation suggested almost complete regression of the breast and axillary mass and regression of liver and lung lesions at 2 years follow-up. The diagnosis of dual malignancy in a patient at the time of first presentation is rare. Recognizing both malignancies at the time of presentation and before initiation of treatment is crucial since the management of these co-existing malignancies is different.

Pivotal role of human stearoyl-CoA desaturases (SCD1 and 5) in breast cancer progression: oleic acid-based effect of SCD1 on cell migration and a novel pro-cell survival role for SCD5

The influence of cell membrane fluidity on cancer progression has been established in different solid tumors. We previously reported that “cancer-associated fibroblasts” (CAFs) induced epithelial-mesenchymal transition and increased cell membrane fluidity and migration in poorly (MCF-7) and highly invasive (MDA-MB-231) breast cancer cells. We also found that the membrane fluidity regulating enzyme stearoyl-CoA desaturase 1 (SCD1) was upregulated in tumor cells co-cultured with CAFs and established its essential role for both intrinsic and CAF-driven tumor cell motility. Here, we further explored the mechanisms involved in the SCD1-based modulation of breast cancer cell migration and investigated the role of the other human SCD isoform, SCD5. We showed that the addition of oleic acid, the main SCD1 product, nullified the inhibitory effects produced on MCF-7 and MDA-MB-231 cell migration by SCD1 depletion (pharmacological or siRNA-based). Conversely, SCD5 seemed not involved in the regulation of cancer cell motility. Interestingly, a clear induction of necrosis was observed as a result of the depletion of SCD5 in MCF-7 cells, where the expression of SCD5 was found to be upregulated by CAFs. The necrotic effect was rescued by a 48-h treatment of cells with oleic acid. These results provide further insights in understanding the role of SCD1 in both intrinsic and CAF-stimulated mammary tumor cell migration, unveiling the metabolic basis of this desaturase-triggered effect. Moreover, our data suggest the ability of CAFs to promote the maintenance of tumor cell survival by the induction of SCD5 levels.

Effect of Needle Size in Ultrasound-guided Core Needle Breast Biopsy: Comparison of 14-, 16-, and 18-Gauge Needles

Introduction: The aim of the present study was to assess the diagnostic accuracy of ultrasound‐guided core needle biopsy (US‐CNB) of breast lesions, comparing smaller needles (16‐ and 18‐gauge) with the 14‐gauge needle, and to analyze the lesion characteristics influencing US‐CNB diagnostic performance. Patients and Methods: All the patients provided informed consent before the biopsy procedure. The data from breast lesions that had undergone US‐CNB in our institution from January 2011 to January 2015 were retrospectively reviewed. The inclusion criterion was the surgical histopathologic examination findings of the entire lesion or radiologic follow‐up data for ≥ 24 months. The exclusion criterion was the use of preoperative neoadjuvant therapy. The US‐CNB results were compared with the surgical pathologic results or with the follow‐up findings in the 3 needle size groups (14‐, 16‐, and 18‐gauge). The needle size‐ and lesion characteristic‐specific diagnostic accuracy parameters were evaluated. Statistical analysis was performed using a dedicated software program, and P ≤ .01 was considered significant. Results: A total of 1118 US‐CNB cases (1042 patients) were included. Of the 1118 cases, 630 (56.3%) were in the 14‐gauge group, 136 (12.2%) in the 16‐gauge, and 352 (31.5%) in the 18‐gauge needle group. Surgery was performed on 800 lesions (71.6%). Of these, 619 were malignant, 77 were high risk, and 104 were benign. The remaining 318 lesions (28.4%) underwent follow‐up imaging studies. All the lesions were stable and, therefore, were considered benign. No differences were observed in the diagnostic accuracy parameters among the 3 needle size groups (P > .01). The false‐negative rate was greater for lesions < 10 mm (7.2%) (P < .01) but without statistically significant differences among the 3 gauges (P > .01). Conclusion: US‐CNB performed with small needles (16 and 18 gauge) had the same diagnostic accuracy as that performed with 14‐gauge needles, regardless of the lesion characteristics. Micro‐Abstract: Our study evaluated the diagnostic accuracy of breast ultrasound‐guided core needle biopsy (US‐CNB), comparing smaller needles (16‐ and 18‐gauge) with the 14‐gauge needle. A total of 1118 US‐CNB cases were retrospectively reviewed, and no differences were observed in the diagnostic accuracy parameters among the 3 needle size groups. US‐CNB performed with smaller needles is a valid alternative to 14‐guage US‐CNB for assessing suspicious breast lesions.

Penile cancer metastasizing to the breast: a case report

BackgroundPenile cancer is a relatively uncommon cancer in developed nations. Metastatic disease is rare, but lymphatic or vascular spreading has been previously reported to the liver, lungs, bones, brain, heart and skin.Case presentationWe report a case of a 49-year-old white man with a penile squamous cell carcinoma previously treated with partial penectomy and bilateral inguinal lymph node dissection, followed by adjuvant therapy. Three years after treatment, the primitive neoplasm metastasized to the breast, presenting as a painful lump. Differentials of a secondary versus a malignant primary tumor were considered and in view of a diagnostic dilemma the lesion was excised.ConclusionsThis case is unusual in its site of metastatic progression as well as in its pattern of clinical presentation. Awareness of such a condition by physicians is mandatory in order to make an early diagnosis and start prompt and correct therapeutic planning.

Stearoyl-CoA desaturase 1 and paracrine signal involvement in the promotion of breast cancer cell migration induced by cancer-associated fibroblasts

Despite the acknowledged impact of the tumor stroma on breast cancer development and progression, the molecular basis of such effects remain partially unexplained. We previously reported that breast cancer-associated fibroblasts (CAFs) induced epithelial-mesenchymal transition and an increase in cell membrane fluidity and migration speed in poorly (MCF-7) and highly invasive (MDA-MB-231) breast cancer cells. More recently, in order to better define the mechanisms responsible for the CAF-promoted tumor cell migration, we investigated the role of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating membrane fluidity, and demonstrated its CAF-triggered up-regulation as well as its crucial role in the migratory ability of the above tumor cells. Besides SCD1 induction, a CAF-promoted enhancement in the protein level and/or activity of the SCD1 transcription factor, the sterol regulatory element-binding protein 1 (SREBP1), was observed. Moreover, the influence of stroma-derived signals in cancer cell migration speed was proved by cell tracking analysis in the presence of neutralizing antibodies to hepatocyte growth factor, transforming growth factor-β or basic fibroblast growth factor, where a marked reduction or abolishment of the fibroblast-triggered increase in cancer cell migration speed was observed. In the last part of this study, in order to verify if soluble CAF-derived factors stimulate breast cancer cell migration in a SCD1-dependent manner, tumor cells were exposed to CAF-conditioned medium (CM) and their migration evaluated by scratch assay in the presence of a small molecule inhibitor of SCD1. Moreover, to assess if the induction of SCD1 expression by CAFs might occur via SREBP1, the desaturase levels were also determined in SREBP1-inhibited tumor cells. These latest investigations indicate that SCD1 contributes to the promotion of breast cancer cell migration by CAF-derived soluble factors, since the desaturase inhibition completely suppressed the stimulatory effect of CAF-CM on tumor cell migration. SREBP1 inhibition impaired CAF-mediated up-regulation of SCD1 in poorly invasive but not in highly invasive tumor cells, in which SREBP1-independent mechanisms may account for the enhancement of SCD1 levels. These results provide further insights in understanding the role of CAFs in promoting tumor cell migration, which may help to design new stroma-based therapeutic strategies.

The Breast Unit and the Organization of Health Care

Breast cancer is acknowledged as an international priority in health care. It is currently the most common cancer in women worldwide, with demographic trends indicating a continuous increase in incidence. Only in the European Union, it is estimated that by 2020 there will be approximately 372,000 new cases of breast cancer per year and 103,000 deaths [1].

Breast cancer stroma influences the migratory behaviour of epithelial malignant cells: the role of secreted hepatocyte growth factor

In breast tumor, interactions occurring between malignant cells and stromal microenvironment heavily influence various aspects of cancer biology. We recently reported that this cross-talk affects structural and functional features correlated with the invasive phenotype of breast cancer cells by co-culturing mammary cancer cells exhibiting different degrees of metastatic potential (MDA-MB-231>MCF-7) with fibroblasts, particularly those isolated from breast tumor stroma (cancer-associated fibroblasts, CAFs). In the present study, we aimed to elucidate some aspects of the epithelium-stroma interaction, related to two linked CAF-triggered effects we previously described: a) increase in cancer cell plasma membrane fluidity; b) increase in speed and directness of cancer cell migration. Thus, we tested the effect of fibroblast/breast cancer cell co-culturing on the expression of Stearoyl-CoA desaturase 1 (SCD1), the main enzyme regulating the fatty acid membrane composition whose up-regulation has been reported in different cancer cells, generally leading to loosely packed membranes. Western blot analysis revealed a dramatic CAF-promoted increase in SCD1 expression in both MCF-7 and MDA-MB-231 cells. Quantitative real-time PCR demonstrated similar variations in the SCD1 transcript levels. With the aim of clarifying the possible role of soluble factors in the CAF-induced increase in speed and directness of cancer cell migration, we performed co-culture assays in presence of a neutralizing antibody against hepatocyte growth factor (HGF) which is released by CAFs and notoriously affects cancer cell motility. We demonstrated that speed and directness increases were strongly reduced or completely abolished by the addition of the anti-HGF neutralizing antibody to the culture medium. These results provide new insights in understanding the role of CAFs, the main host stromal component of breast cancer, in promoting the tumor cell invasive attitude and may help in defining further promising therapeutic targets.