Is routine axillary lymph node dissection needed to tailor systemic treatments for breast cancer patients in the era of molecular oncology? A position paper of the Italian National Association of Breast Surgeons (ANISC).

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) management began when sentinel lymph node biopsy (SLNB) replaced axillary lymph node dissection (ALND) as standard of care in patients with node-negative BC. The second step consolidated ALND omission in selected subgroups of BC patients with up to two macrometastases and recognized BC molecular and genomic implication in predicting prognosis and planning adjuvant treatment. Outcomes from the recent RxPONDER and monarchE trials have come to challenge the previous cut-off of two SLN in order to inform decisions on systemic therapies for hormone receptor-positive (HR+), human epidermal growth factor receptor type-2 (HER2) negative BC, as the criteria included a cut-off of respectively three and four SLNs. In view of the controversy that this may lift in surgical practice, the Italian National Association of Breast Surgeons (Associazione Nazionale Italiana Senologi Chirurghi, ANISC) reviewed data regarding the latest trials on this topic and proposes an implementation in clinical practice. MATERIAL AND METHODS: We reviewed the available literature offering data on the pathological nodal status of cN0 breast cancer patients. RESULTS: The rates of pN2 status in cN0 patients ranges from 3.5 % to 16 %; pre-surgical diagnostic definition of axillary lymph node status in cN0 patients by ultrasound could be useful to inform about a possible involvement of ≥4 lymph nodes in this specific sub-groups of women. CONCLUSIONS: The Italian National Association of Breast Surgeons (ANISC) considers that for HR + HER2-/cN0-pN1(sn) BC patients undergoing breast conserving treatment the preoperative workup should be optimized for a more detailed assessment of the axilla and the technique of SLNB should be optimized, if considered appropriate by the surgeon, not considering routine ALND always indicated to determine treatment recommendations according to criteria of eligibility to RxPONDER and monarch-E trials.

"OPERATION PHALCO"-Adapted Physical Activity for Breast Cancer Survivors: Is It Time for a Multidisciplinary Approach?

The international literature emphasizes the importance of physical activity (PA) in the first steps after cancer surgery. The regular practice of physical exercise causes positive adaptations on several functional capacities, with positive consequences on patients' quality of life. This project aims to evaluate the effect of a post-operative training protocol, structured by taking into account both cancer-related issues and the presence of comorbidities, on functional capacities and quality of life of breast cancer survivors. Therefore, it was necessary to create a synergy between oncologists (referring physicians), sport medicine physicians (risk stratification and exercise prescription) and kinesiologists (trainers). Thirty-five post-surgery BC patients decided on a voluntary basis to attend an online Adapted PA (APA) protocol for 4 months, twice a week (APA Group) or Usual Care Group (UC Group). Functional capacity of the APA Group significantly increased, by 13.1% (p = 0.000), whereas perceived exertion decreased by 19.7% (p = 0.020). In the same group, the general health evaluated through the questionnaire EORTC-QLQ-C30 increased (p = 0.050). No differences were found in the UC Group. Operation Phalco, creating a network between oncologists, sports medicine physicians and kinesiologists, confirms the importance of structuring a post-operative path where APA should be included as early as possible in the cancer patient care.

Adjuvant aromatase inhibitor therapy in early breast cancer: what factors lead patients to discontinue treatment?

BACKGROUND: Aromatase inhibitors (AIs) are standard hormone therapy (HT) for the adjuvant treatment of postmenopausal endocrine-sensitive early breast cancer. Treatment discontinuation due to toxicity is an important issue that may help clinicians identify effective clinical interventions to allow adequate treatment duration. We reviewed the main reasons for interruption of AIs at our institution from 2006 to 2009. METHODS: 236 patients treated with adjuvant AIs were eligible for analysis. Median age was 64 years (35-89), median follow-up 53 months (6-60). Prior adjuvant chemotherapy was taxane based in 47 patients and anthracycline based in 43 patients. 118 patients had received letrozole, 101 anastrozole, and 17 exemestane. RESULTS: Twenty-four patients (10%) needed discontinuation of the first AI assigned as a result of toxicity. Grade 2/3 arthralgia was the main reason for discontinuation in 13/24 patients. No differences in the incidence of arthralgia were noted in patients who had received taxanes or anthracyclines. Headache, alopecia, itching, diffuse skin reaction, allergic reaction with hypertensive crisis, xerostomia and xerophthalmia, insomnia and somnolence were the other reasons for discontinuation. In multivariate logistic regression analysis, age (65 years) and HT were independent factors associated with the onset of arthralgia (p = 0.006 and p = 0.008, respectively; OR 2.65, 95% CI 1.32-5.31). Alternative HT (AI or tamoxifen) was offered to patients who wanted or needed to permanently interrupt the ongoing drug. CONCLUSIONS: In our analysis, 10% of patients discontinued the first AI assigned because of toxicity. Median time course of all adverse events leading to HT discontinuation was 155 days and 135 days for arthralgia. A switch to alternative HT with toxicity monitoring is a recommended option for avoiding premature and permanent interruption of an effective treatment.

Epirubicin and docetaxel as first-line treatment for hormonal receptor positive metastatic breast cancer: the predictive value of luminal subtype: a retrospective cohort analysis.

BACKGROUND: We retrospectively evaluated the efficacy of first-line epirubicin and docetaxel in patients with metastatic, hormonal receptor (HR)-positive, and human epidermal growth factor receptor-2-negative breast cancer. A subgroup analysis evaluated the predictive value of immunohistochemistry-defined luminal subtype. METHODS: We included patients with at least one visceral and measurable site of metastatic disease. Patients were grouped as luminal A (HR(+) and Ki67<13%) or luminal B (HR(+) and Ki67>13%). RESULTS: Forty-four patients were entered and prognostic variables were similar between the subgroups. Luminal B patients achieved higher objective response rate than luminal A (69% versus 19%; P = 0.001), longer time to progression (12.2 months versus 8.6 months; P = 0.039), and longer overall survival (24.6 months versus 19.5 months; P = 0.041). The multivariate analysis confirmed the predictive value of luminal B subtype for longer time to progression. CONCLUSIONS: Identification by Ki67 labelling index of human epidermal growth factor receptor-2-negative luminal A could predict a substantial benefit from systemic chemotherapy. Endocrine therapy would be the most appropriate therapy for luminal A tumours.

Gemcitabine and carboplatin for pretreated metastatic breast cancer: the predictive value of immunohistochemically defined subtypes.

BACKGROUND: We evaluated the efficacy of gemcitabine and carboplatin for patients affected by pretreated metastatic breast cancer. A subgroup analysis was performed to evaluate the predictive value of immunohistochemically defined breast cancer subtypes. METHODS: We included human epidermal growth factor 2 (HER-2) negative metastatic breast cancer resistant to previous anthracycline-based and taxane-based chemotherapy, and HER-2 positive metastatic breast cancer with at least two progressions of disease during protracted trastuzumab-based therapy. Treatment consisted of gemcitabine (1000 mg/m(2) intravenous (iv) on days 1 and 8) and carboplatin (area under the curve 5 iv on day 1) applied every 3 weeks. RESULTS: Forty-two patients were registered. Disease control was 58%, with a median time-to-progression (TTP) of 7 months (range 1-12) and a median overall survival of 10.5 months (range 1-34). Patients were grouped as triple negative (ER and PR negative, HER-2 negative), HER-2 (HER-2 positive, ER and PR negative), luminal B (ER and/or PR positive and either HER-2 positive and/or high Ki67), and luminal A (ER and/or PR positive and HER-2 negative and low Ki67). For luminal A patients, disease control was lower (luminal A 34 vs. others 67%; P = 0.02), TTP was shorter (luminal A 2.4 months vs. others 6.3 months, P = 0.015), and overall survival was shorter (luminal A 7.5 months vs. others 11.7 months, P = 0.034) than for other subtypes. CONCLUSIONS: Gemcitabine and carboplatin are effective for pretreated patients with metastatic breast cancer. Luminal A subtype seems to fare poorly compared with other subtypes. Specific difference in gene expression might account for the different outcome.

[Gastrointestinal stromal tumours: a case report and review of the literature]. / Tumori stromali gastrointestinali (GIST): descrizione di un caso clinico e revisione della letteratura.

Gastrointestinal stromal tumours are a heterogeneous group of neoplasms of the digestive apparatus characterised by a complex histogenesis and lines of differentiation that make it difficult to predict their biological behaviour. Expression of the c-kit receptor in about 99% of gastrointestinal stromal tumours suggests they may originate from a common mesenchymal element with a variable possibility of phenotypical differentiation. The Authors report a case of small bowel gastrointestinal stromal tumour referred to them for severe bleeding and treated surgically. They then go on to analyse the diagnostic and therapeutic problems that such tumours entail. Surgery is currently the only therapeutic option capable of improving survival in patients with gastrointestinal stromal tumours. Further studies are needed to assess the efficacy of laparoscopy and new chemotherapeutic agents.

[Intestinal duplication in the adult. A case report of colonic duplication and a review of the literature]. / La duplicazione intestinale nell'adulto. Descrizione di un caso di duplicazione del colon e revisione della letteratura.

Alimentary tract duplications are uncommon congenital anomalies that are usually present during the first decade of life. However, a smaller number of cases may remain unsuspected until adulthood. They are most common in the ileum but can occur anywhere along the alimentary tract. Duplications may be cystic or tubular in appearance and characteristically arise from the mesenteric aspect of the intestine. Abdominal pain, nausea and/or vomiting, palpable mass, weight loss, and bleeding are the most common symptoms. This paper reports the case of a 24-year-old male with a cystic duplication of the ascending colon not correctly diagnosed prior to operation. When faced with such an abdominal cystic lesion, differential diagnoses versus duplication cyst, mesenteric cyst, choledochal cyst, giant diverticulum, and cystic tumour of the pancreas should be considered. Ultrasound and computerized tomography are good tools for diagnosis and for delineating the relationship between the cyst and peripheral structures. Surgery provides treatment and allows a final pathological diagnosis. Removal of the cyst could be considered satisfactory but resection of the duplication and the adjacent bowel is recommended because of the possibility of malignant degeneration and the risk of gastrointestinal ulceration and haemorrhage due to ectopic gastric mucosa.