Rassegna della letteratura – marzo 2019

Trattamento loco-regionale

(chirurgia oncologica, chirurgia  plastica-ricostruttiva, radioterapia)

Faisal M, Fathy H, Gomaa AMM et Al. – Breast cancer involvement of the nipple-areola complex and implications for nipple-sparing mastectomies: a retrospective observational study in 137 patients. – Patient Saf Surg. 2019 Mar 16;13:15. doi: 10.1186/s13037. eCollection 2019.

Background: Nipple-sparing mastectomy (NSM) has gained much attention by enhancing the aesthetic outcome in breast carcinoma patients. The aim of this study was to assess the prevalence of malignant affection of the nipple-areola complex (NAC) in breast carcinoma patients and its correlation with prognostic factors for breast cancer.

Methods: This study included 137 female patients diagnosed with breast carcinoma at different disease stages who were admitted to our surgical oncology unit at Suez Canal University Hospital from June 15, 2014 to January 25, 2017. We excluded patients with evidence of nipple involvement as ulceration or patients with previous breast surgery with periareolar incisions. This study was designed to test the hypothesis that the NAC can be spared in certain selected patients. All studied participants provided a full history and underwent general and local clinical examinations, pre-operative laboratory tests, and radiological and pathological evaluations.

Results: The mean age of the study population was 47.39 ± 8.01 years. Among the patients, the NAC was affected in 12 (11.40%) patients. Patients with NAC involvement showed a significantly larger tumor size of more than 4 cm and a shorter tumor-nipple distance of less than 2 cm (p = 0.000). Lymph node metastasis was associated with NAC involvement (p = 0.001), with increased risk when more than 10 lymph nodes were involved (p = 0.007). Lymphovascular invasion was a significant predictor of NAC involvement (p = 0.014). Multifocal as well as multicentric tumors were significantly associated with NAC involvement (p = 0.016 and 0.003, respectively). NAC involvement was more likely in Estrogen receptor (ER) and Progesterone receptor (PR) patients than in ER+ and PR+ patients (p = 0.000), while Human epidermal receptor (HER+) patients were more likely to have NAC involvement than HER patients (p = 0.000). Additionally, stage ΙΙΙ cancer was significantly associated with NAC involvement (p = 0.041), and histological grade III disease carried a greater risk than grade I disease of NAC involvement (p = 0.008).

Conclusion: The incidence of NAC affection among breast carcinoma patients who underwent mastectomy and axillary clearance was associated with important parameters, such as tumor size, areola edge-tumor distance, lymph node affection, hormonal receptor status and lymphovascular invasion. Accordingly, NAC-preserving surgeries could be tailored to patients with favourable tumor characteristics.

Bathily T, Borget I, Rivin Del Campo E et Al. – Partial versus whole breast irradiation: Side effects, patient satisfaction and costs. – Cancer Radiother. 2019 Mar 28. pii: S1278-3218(19)30028-9.

Background: Since accelerated partial breast irradiation has demonstrated non-inferiority to whole breast irradiation regarding recurrence rate in patients with early stage breast cancer, our objective was to compare its impact on short-term adverse events, patient satisfaction and costs.

Methods: Patients with early stage breast cancer treated by breast-conserving surgery between 2007 and 2012 were included: 48 women who received three-dimensional conformal accelerated partial breast irradiation in a multicentre phase-II trial were paired with 48 patients prospectively treated with whole breast irradiation. Adverse events, and patients’ opinions concerning cosmesis, satisfaction and pain, were gathered 1 month after treatment. Direct and indirect costs were collected from the French National Health Insurance System perspective until the end of radiotherapy.

Results: When comparing its impact, skin reactions occurred in 37% of patients receiving three-dimensional conformal accelerated partial breast radiotherapy and 60% of patients receiving whole breast irradiation (P=0.07); 98% were very satisfied in the group three-dimensional conformal accelerated partial breast radiotherapy versus 46% in the group treated with whole breast irradiation (P<0.001); direct costs were significantly lower in the group treated with partial breast irradiation (mean cost: 2510€ versus 5479€/patient), due to less radiation sessions

Conclusion: In patients with early-stage breast cancer, partial irradiation offered a good alternative to whole breast irradiation, as it was less expensive and satisfactory. These, and the clinical safety and tolerance results, need to be confirmed by long-term accelerated partial breast irradiation results in on-going phase III trials.

Korzets Y, Fyles A, Shepshelovich D et Al.. – Toxicity and clinical outcomes of partial breast irradiation compared to whole breast irradiation for early-stage breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019 Mar 30. doi: 10.1007/s10549-019-05209-9.

Background: There is uncertainty about outcomes differences between partial breast irradiation (PBI) and whole breast irradiation (WBI) for early-stage breast cancer.

Methods: Prospective randomized trials comparing adjuvant PBI to WBI in early-stage invasive breast cancer were identified using PubMed. Odds ratios (OR), 95% confidence intervals and absolute risks were computed for pre-specified efficacy and toxicity outcomes including cosmesis. Subgroup analysis evaluated the effect of PBI modality (external beam radiation treatment [EBRT], intraoperative radiation treatment [IORT] or brachytherapy) on efficacy. Meta-regression analysis explored the influence of median follow-up, patient and tumor characteristics on results.

Results: Nine trials comprising 14514 patients were included. While PBI was associated with increased odds of local recurrence compared to WBI (OR 1.69, P < 0.001), it was associated with reduced odds of death without breast cancer recurrence (OR 0.55, P < 0.001) and with improvement in overall survival (OS) that approached, but did not meet statistical significance (OR 0.84, P = 0.06). Subgroup analysis for PBI modality showed significant differences in the odds of local recurrence, based on method of PBI with EBRT showing the lowest magnitude of inferiority. Nodal involvement was associated with higher local recurrence risk, while larger tumors were associated with lesser improvement in death without breast cancer recurrence and OS. PBI was associated with higher odds of fat necrosis (OR 1.72, P = 0.002). Worse cosmetic outcome with PBI approached statistical significance (OR 1.23, P = 0.06).

Conclusion: Compared to WBI, PBI is associated with higher odds for local recurrence and toxicity, but less death without breast cancer recurrence. The balance between benefit and risk of PBI appears optimal for women with smaller hormone receptor positive tumors, without nodal involvement and treated with EBRT.

Garcia-Etienne CA, Mansel RE, Tomatis M et Al. – Trends in axillary lymph node dissection for early-stage breast cancer in Europe: Impact of evidence on practice.Breast. 2019 Mar 11;45:89-96. doi: 10.1016/j.breast.2019.03.002.

Background: Data from recently published trials have provided practice-changing recommendations for the surgical approach to the axilla in breast cancer. Patients with T1-2 lesions, treated with breast conservation, who have not received neoadjuvant chemotherapy and have 1-2 positive sentinel nodes (Z0011-criteria) may avoid axillary lymph node dissection (ALND). We aim to describe the dissemination of this practice in Europe over an extended period of time.

Methods: Our source of data was the eusomaDB, a central data warehouse of prospectively collected information of the European Society of Breast Cancer Specialists (EUSOMA). We identified cases fulfilling Z0011-criteria from 2005 to 2016 from 34 European breast centers and report trends in ALND. Data derived from Germany, Italy, Belgium, Switzerland, Austria, and Netherlands.

Results: 6671 patients fulfilled Z0011-criteria. Rates of ALND showed a statistically significant decrease from 2010 (89%) to 2011 (73%), reaching 46% in 2016 (p < 0.001). After multivariable analysis, factors associated with higher probability of ALND were earlier year of surgery, younger age, increasing tumor size and grade, and being operated in Italy (p < 0.001). The minimum and maximal rates of ALND in the most recent two-year period (2015-2016) were 0% and 83% in two centers located in different countries (p < 0.001).

Conclusion: Our study demonstrates, a decrease in rates of ALND that started after year 2010 through the end of the study period. Wide differences were observed among centers and countries indicating the need to spread unified clinical guidelines in Europe to allow for homogeneous evidence-based practice patterns

Zwicker F, Kirchner C, Huber PE et Al.Breast cancer occurrence after low dose radiotherapy of non-malignant disorders of the shoulder. – Sci Rep. 2019 Mar 28;9(1):5301. doi: 10.1038/s41598-019-41725-w.

Stochastic long-term damages at relatively low doses have the potential for cancer induction. For the first time we investigated the occurrence of breast cancer in female patients after radiotherapy of non-malignant disorders of the shoulder and made a comparison with the estimated spontaneous incidence of mammary carcinoma for this cohort. In a geographically defined district with a population of approximately 100.000 inhabitants, comprehensive data of radiological diagnostics and radiotherapy were registered nearly completely for 41 years; data included mammography and radiotherapy of breast cancer patients as well as of non-malignant disorders. Within this population a collective of 158 women with radiotherapy of the shoulder was investigated. Radiotherapy was performed with cobalt-60 photons (Gammatron) with an average cumulative-dose of 6 Gy. The average follow-up time was 21.3 years. Patients were 55 years old (median) when radiotherapy of the shoulder was performed. Seven patients (4.4%) developed breast cancer after a median of 21 years. According to the incidence statistics, 9.4 +/- 1.8 (95%CI) cases (5.9%) would be expected. In regard to the irradiated shoulder neither the ipsilateral nor the contralateral breasts showed increased rates of breast cancer. An induction of additional breast cancer caused by radiation of non-malignant disorders of the shoulder wasn’t detected in the investigated cohort.

Lynn JV, Urlaub KM, Ranganathan K et Al.“The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety”. Plast Reconstr Surg. 2019 Mar 7. doi: 10.1097/PRS.0000000000005647.

Background: Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine is an FDA-approved iron chelator with immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study is to determine the impact of deferoxamine on breast cancer cell proliferation in-vitro, to delineate oncologic safety concerns regarding the utilization of deferoxamine as a regenerative therapeutic.

Methods: The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined via MTS (percent cell viability) and tumorsphere (sphere number) analysis. Radiation (0, 5, and 10Gy) and deferoxamine (0, 25, 50, 75, and 100µM) were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, NF-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. ANOVA statistical analysis was performed using SPSS (p<0.05).

Results: For both cell lines, percent viability and sphere number significantly decreased following exposure to 10Gy of radiation. Surprisingly, the administration of 25µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100µM) in combination with radiation (10Gy) resulted in significantly reduced percent viability and sphere number compared to the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed NF-κB activation, and induced apoptosis.

Conclusion: Radiation and deferoxamine significantly decrease breast cancer cell proliferation when delivered independently and in combination, suggesting deferoxamine may be safely utilized to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors.

Dinas K, Kalder M, Zepiridis L et Al. – Axillary web syndrome: Incidence, pathogenesis, and management. – Curr Probl Cancer. 2019 Mar 15. pii: S0147-0272(18)30348-9. doi: 10.1016/j.currproblcancer.2019.02.002

Axillary web syndrome (AWS) refers to the development of fibrotic bands or “cords” in the axilla of patients who have undergone axillary lymph node dissection for breast cancer. We review the incidence, pathogenesis, risk factors, and management of AWS. AWS is a common complication in patients who undergo axillary lymph node dissection. Even though AWS is self-limited in most cases, it causes significant morbidity. The optimal management of AWS is unclear but physiotherapy appears to be beneficial. The widespread use of less invasive procedures to evaluate the presence of metastasis in the axillary lymph nodes (ie, sentinel lymph node biopsy) is expected to reduce the incidence of AWS. The close collaboration of surgeons, oncologists, and physiotherapists is necessary for the prevention and management of this frequent condition