Multidisciplinary and Tailored Treatment of Locally Advanced Breast Cancer in Progression during Neoadjuvant Chemotherapy: Case Report.

Locally advanced breast cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognized, a small number of patients show Progressive Disease (PD). No standard salvage treatment (ST) has been defined and different strategies can be adopted, such as second-line systemic therapies, radiation therapy, and surgery. Herein, a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment for each patient.

Oncoplastic level II volume displacement surgery for breast cancer: oncological and aesthetic outcomes.

Oncoplastic breast-conserving surgery (OBCS) is increasingly used to treat breast cancer with the dual purpose of performing a radical oncological resection while minimizing the risk of post-operative deformities. The aim of the study was to evaluate the patient outcomes after Level II OBCS as regards oncological safety and patient satisfaction. Between 2015 and 2020, a cohort of 109 women consecutively underwent treatment for breast cancer with bilateral oncoplastic breast-conserving volume displacement surgery; patient satisfaction was measured with BREAST-Q questionnaire. The 5-year overall survival and disease-free survival were 97% (95%CI 92, 100) and 94% (95%CI 90, 99), respectively. In two patients (1.8%), mastectomy was finally performed due to margin involvement. The median patient-reported score for "satisfaction with breast" (BREAST-Q) was 74/100. Factors associated with a lower aesthetic satisfaction index included: location of tumour in central quadrant (p = 0.007); triple negative breast cancer (p = 0.045), and re-intervention (p = 0.044). OBCS represents a valid option in terms of oncological outcomes for patients otherwise candidate to more extensive breast conserving surgery; the high satisfaction index also suggests a superiority in terms of aesthetic outcomes.

A Case of Life-Threatening Bleeding Due to a Locally Advanced Breast Carcinoma Successfully Treated with Transcatheter Arterial Embolization.

Locally advanced breast cancer (LABC) may rarely present with acute severe bleeding. A case report dealing with transcatheter arterial embolization to control acute bleeding in a patient with a voluminous ulcerated breast mass is described. Our findings confirm that the endovascular approach is effective in such patients in order to stabilize the patient whenever conventional treatments have failed or bleeding may be life-threatening.

Inferior Pedicle Reduction Mammoplasty as Corrective Surgery after Breast Conserving Surgery and Radiation Therapy.

Background/Aim-Twenty patients had corrective reconstruction surgery by means of a reduction mammaplasty or mastopexy after a previous BCS (Breast Conserving Surgery) and RT (Radiation Therapy); the risk factors and post-operative complications were reported in order to define a safe and effective technique for reduction mammaplasty in previously irradiated breast cancer patients. Materials and Methods-From June 2011 to December 2019, 20 pts. were operated on at the Breast Surgery Clinic of San Martino Policlinic Hospital, Genoa, Italy. Pre- and post-operative parameters included clinic-pathological features of the primary tumor; a lapse of time from primary radio-surgery; the extent of follow-up; the rate of post-operative wound infections; the persistence of breast asymmetry, and a post-operative patient satisfaction index by means of a BREAST-Q questionnaire. Results-Three patients (15%) developed minor complications in the irradiated breast, but no complication was observed into the non-irradiated breast. No statistically significant correlation was found between the post-operative complications and the risk factors. The statistical analysis of BREAST-Q questionnaire responses gave an average patient's satisfaction index that was equal to 90.8/100 (range: 44 to 100). Conclusions-Inferior pedicle reduction mammoplasty is an effective reduction mammoplasty technique in regard to the extent of breast tissues that are to be removed both in irradiated and contralateral breast; moreover, the incidence of post-operative complications is clearly limited when a careful technique is adopted, and it can be reasonably applied also in patients with co-morbidity factors.

"No Ink on Tumor" in Breast-Conserving Surgery after Neoadjuvant Chemotherapy.

Background/Aim: Patients with Stage I-II breast cancer undergoing breast-conserving surgery after neoadjuvant chemotherapy (BCS-NAC) were retrospectively assessed in order to evaluate the extent of a safe excision margin. Materials and Methods: Between 2003 and 2020, 151 patients underwent risk-adapted BCS-NAC; margin involvement was always assessed at definitive histology. Patients with complete pathological response (pCR) were classified as the RX group, whereas those with residual disease and negative margins were stratified as R0 < 1 mm (margin < 1 mm) and R0 > 1 mm (margin > 1 mm). Results: Totals of 29 (19.2%), 64 (42.4%), and 58 patients (38.4%) were included in the R0 < 1 mm, R0 > 1 mm, and RX groups, respectively, and 2 patients with margin involvement had a mastectomy. Ten instances of local recurrence (6.6%) occurred, with no statistically significant difference in local recurrence-free survival (LRFS) between the three groups. A statistically significant advantage of disease-free survival (p = 0.002) and overall survival (p = 0.010) was observed in patients with pCR. Conclusions: BCS-NAC was increased, especially in HER-2-positive and triple-negative tumors; risk-adapted BCS should be preferably pursued to highlight the cosmetic benefit of NAC. The similar rate of LRFS in the three groups of patients suggests a shift toward the "no ink on tumor" paradigm for patients undergoing BCS-NAC.

The Margins' Challenge: Risk Factors of Residual Disease After Breast Conserving Surgery in Early-stage Breast Cancer.

BACKGROUND/AIM: Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome. PATIENTS AND METHODS: A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD). RESULTS: RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p<0.001); the corresponding contribution to the prognostic score was as follows: close margins, 3 points; hormone receptor positive disease, 2 points; low Ki67, 2 points; HER2 negativity, 1 point. In 102 patients with a score >3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p<0.001). CONCLUSION: This predictive model might aid in clinical-decision making of patients with positive margins who actually require a widening procedure after intraoperative and/or definitive histology.

Tumor-to-nipple Distance Should Not Preclude Nipple-sparing Mastectomy in Breast Cancer Patients. Personal Experience and Literature Review.

BACKGROUND/AIM: A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin. PATIENTS AND METHODS: Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR). RESULTS: Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p<0.003) and excision margins less than 2 mm (p<0.000). Eleven retroareolar specimens were positive at definitive pathology; final re-excision specimen examination showed residual disease in seven patients (63.6%). At a median follow-up of 31 to 33 months, no NAC recurrence did occur; disease-free survival was more than 96%, and LRR was homogeneously distributed among TND subgroups. CONCLUSION: Therapeutic NSM is a safe procedure independently of TND assessed at preoperative breast MRI. Permanent section assessment of retroareolar tissue is more accurate and cost-effective than frozen section. Furthermore, delayed nipple and/or NAC excision did not impair local disease control.

The Role of Sentinel Lymph Node Biopsy in Patients With B5c Breast Cancer Diagnosis.

BACKGROUND/AIM: The histopathological assessment of the B5c category may sometimes be hampered by simple artifacts that may lead to over- or underestimation of that particular breast cancer so that its management is still controversial, especially with regard to the decision to proceed immediately to sentinel lymph node (SLN) biopsy. Hence, a retrospective study was performed in 174 patients undergoing breast-conserving surgery with a preoperative diagnosis of B5c in order to assess the usefulness of axillary node staging by means of SLN biopsy. PATIENTS AND METHODS: Pre- and post-operative parameters including imaging data, histology of the primary tumor and SLN biopsy, biological prognostic factors, type of operation, and adjuvant regimens were computed. RESULTS: Invasive carcinoma and carcinoma in situ were diagnosed in 46 (26.5%) and 128 patients (73.5%), respectively. Preoperative tumor size was significantly related to post-operative diagnosis of invasive carcinoma (p=0.020), retaining its predictive value at logistic regression analysis (p=0.046). Post-operative predictive factors of invasion were represented by tumor stage (p=0.008) and grading (p=0.008). CONCLUSION: B5c preoperative diagnosis in patients undergoing breast conservative surgery would suggest an immediate wide local excision avoiding any further preoperative histologic assessment. Conversely, one-stage SLN biopsy might be suggested for patients eligible to mastectomy, similar to patients with carcinoma in situ, although its impact on the therapeutic and prognostic assessment seems negligible.

Integrated Treatment With Stapled Haemorrhoidopexy and Proctonorm® of Haemorrhoidal Disease.

BACKGROUND/AIM: This retrospective study was performed in patients undergoing Stapled Haemorrhoidopexy (SH) who were post-operatively treated with Proctonorm® with the aim of assessing its effect on early and late haemorrhoidal-related symptoms. PATIENTS AND METHODS: Forty-six males and 54 females received Proctonorm® (one tablet twice daily for 14 days) and Ketoprofene R (200 mg, one tablet twice daily, as requested). RESULTS: "Early Complication Score" (0-12) two days after surgery was 2.02±1.03; pain VAS (Visual Analogue Scale) (0-10) was 1.21±0.89, and the number of anti-inflammatory tablets was 4.24±1.06. At 40-day post-operative assessment, seven patients had post-operative complications with "Late Complication Score" (0-20) of 0.34±0.68. At six-month follow-up, a high index of patient satisfaction (VAS=9.39±0.24) was self-reported with 75% reduction in CSS (Constipation Scoring System) (1.95±2.58) compared to preoperative scores; "Late Complication Score" was 0. CONCLUSION: The specific target activity of Proctonorm® at the microcircular level may be effective in patients undergoing SH in order to reduce the inflammatory response of residual haemorrhoids while waiting for stable resolution of symptoms within one or two weeks.

No Ink on Ductal Carcinoma In Situ: A Single Centre Experience.

BACKGROUND/AIM: A retrospective analysis of 388 patients with pure ductal carcinoma in situ (DCIS) was performed in order to test the correlation of clearance margin of resection and other host-, tumor- and treatment-related factors with ipsilateral breast tumor recurrence (IBTR). MATERIALS AND METHODS: The pathological analysis was performed according to a standardized protocol: positive margins had DCIS at the inked margin; close margins had tumor between 0.1 to 0.9 mm, or 1 to 1.9 mm, and negative margins were ≥2 mm. RESULTS: At a median follow-up of 90 months there were 26 IBTR (10 invasive and 16 DCIS). Both in univariate and multivariate analysis a significant difference was observed in IBTR by comparing positive versus close/negative margins of excision (p=0.05) and the number of re-operations (p=0.000). Moreover, the actuarial IBTR rates were significantly different in patients with a positive compared to close/negative margins (log-rank test, p=0.042) while the stratification by the margin width (0.1-0.9 mm; 1.0-1.9 mm; ≥2 mm) was not significant (log-rank test, p=0.243). CONCLUSION: The policy of "no ink on the tumor" can be translated from invasive to DCIS, because the actuarial IBTR rates were significantly different only in patients with a positive, compared to close/negative margins.

Tumescent Anesthesia in Skin- and Nipple-sparing Mastectomy: Results of a Prospective Clinical Study.

BACKGROUND: The tumescent mastectomy technique has been used to facilitate dissection of subcutaneous tissue and mammary gland in order to reduce intraoperative bleeding and speed the operation. PATIENTS AND METHODS: A prospective clinical study was performed on 30 female patients undergoing immediate breast reconstructions after skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM) in order to assess early postoperative complications, pain, and final esthetic outcome of skin flaps related to tumescent anesthesia (TA). RESULTS: TA significantly speeded-up the operative procedure (131±49.99 vs. 180.5±67.15 min; p=0.03) achieving less skin damage compared to patients who did not have TA (p=0.045); moreover, no significant difference occurred with regard to the length of in-hospital stay and overall lymphatic drainage. CONCLUSION: The length of the operation as well as the final cosmetic outcome of skin flaps was significantly improved due to TA, with no appreciable side-effects.

Axillary ultrasound and Fine-Needle Aspiration Cytology in the preoperative staging of axillary node metastasis in breast cancer patients.

OBJECTIVE: A prospective observational clinical study was undertaken to assess the accuracy of preoperative Axillary Ultrasound (AUS) plus Fine-Needle Aspiration Cytology (FNAC) as well as and its clinical utility, that is the capacity of the information supplied by the test to guide the clinical decision-making. MATERIALS AND METHODS: from January 2013 to August 2015, 400 female patients with pT1-3 cN0 operable breast cancer underwent AUS with FNAC at the Breast Unit of the "IRCCS San Martino-IST" in Genoa (Italy). RESULTS: 127 out of 400 patients (31.7%) had axillary lymph node metastases; in 69 out of 127 node-positive patients (54.3%) AUS detected at least one abnormal lymph node, and in 56 out of 127 patients (44.1%) the abnormal sonographic pattern of the lymph node was coupled with a positive FNAC finding. No false-positive finding by both AUS-alone or combined AUS/FNAC was observed. AUS-alone had sensitivity of 54.3% (69/127), specificity of 100% (273/273), PPV of 100% (69/69), NPV of 82.5% (273/331), and accuracy of 85.5% (342/400). Combined AUS/FNAC had sensitivity of 44.1% (56/127), specificity of 100% (273/273), PPV of 100% (56/56), NPV of 79.4% (273/344), and accuracy of 82.2% (329/400). CONCLUSIONS: AUS-alone or combined AUS/FNAC had a high accuracy rate coupled with a more than satisfactory efficiency due to their low costs and easy access for the preoperative staging of the axilla. Notably, AUS-alone might be suggested for the preoperative staging of patients with early stage breast cancer because FNAC did not increased the specificity but reduced the sensitivity of the technique. Patients with negative findings might undergo either SLNB or close observation while waiting for the definitive results of ongoing SOUND randomized clinical trial.

Predictive factors of non-sentinel lymph node involvement in patients with invasive breast cancer and sentinel node micrometastases.

Patient-related, tumor-related, and sentinel node (SN)-related factors have been identified with the aim of predicting non-SN status in patients with SN micrometastases. According to our previous experience, primary tumor size (p=0.005) and the presence of lymphovascular invasion (LVI) (p=0.000) significantly predicted non-SN status in patients with SN micrometastasis; moreover, non-SN metastases were never detected in patients with pT1a-1b, G1, and no LVI. A prospective assessment was undertaken in a validation set of 126 patients to confirm these findings. Univariate analysis indicated that primary tumor size (p=0.05), Scarff-Bloom-Richardson (SBR) grade (p=0.008), LVI (p=0.001), and the number of mitoses/mm(2) (p=0.01) were significant predictors of non-SN status. By logistic regression analysis, tumor size (p=0.03), LVI (p=0.001), grade (p=0.003) and the number of mitoses/mm(2) (p=0.01) were the only variables remaining in the model. Three subsets of patients were identified: i) 18.3% of patients (pT1, G1, and no LVI) had tumor-negative non-SN (no risk group); ii) 37.3% of patients (number of mitoses/mm(2) <10, SBR grade II-III) had a rate of tumor-positive non-SN <15% (intermediate risk); iii) 44.4% of patients had a mean rate of non-SN involvement of 46% (high risk). By these parameters, more than 50% of patients could be selectively spared unnecessary axillary lymph node dissection without staging or therapeutic benefit, especially in patients with well-differentiated pT1 tumors without LVI.