Occult breast cancer presenting as axillary lymph node metastases: a single-institution experience with a challenging diagnostic and therapeutic dilemma

Background: Occult breast cancer with axillary lymph node metastases but without evidence of primary tumor on clinical examination and conventional imaging is a rare but serious scenario. Due to diagnostic difficulties and prognostic uncertainties, evidence to guide the management of such patients is lacking. Here, we review the cases of occult breast cancer treated at our institution and discuss recent advances in its management. Methods: We searched our database for patients with occult breast cancer operated on between 2002 and 2011. The following data were extracted: clinical presentation; diagnostic work-up; surgical treatment; adjuvant management; and duration of follow-up. Results: Out of 1405 patients operated on for breast cancer, 7 (0.5%) had occult breast cancer. The mean age at diagnosis was 60.5 years. Six patients were postmenopausal. All patients had one or more metastatic axillary lymph nodes but no signs of malignancy at either conventional imaging (mammography and ultrasonography) or clinical examination. Magnetic resonance imaging revealed the primary breast tumor in 1 patient. Histopathology showed positive estrogen receptors in 3 patients. After preoperative staging, neoadjuvant chemotherapy and subsequent mastectomy was performed in 1 patient with N3 disease, primary surgical treatment in 5 patients (4 mastectomies, 1 breast-conserving procedure), and chemotherapy alone in 1 patient. Postoperative management included chemotherapy in 5 patients, endocrine therapy in 2, and radiation therapy in 5. An infiltrating carcinoma was found in 5 mastectomy specimens (4 ductal histotype and 1 lobular histotype). The mean tumor size was 11 mm (range, 7-17). At a mean follow-up of 51 months, 6 patients were disease-free, and 1 patient died of pulmonary embolism. Conclusions: Occult breast cancer poses difficult management issues, especially when estrogen receptor status is negative. No consensus exists on the need for breast surgery in such patients, as recent literature suggests that breast irradiation might be an alternative treatment. Management decisions should be taken on an individual basis with a multidisciplinary approach. Considering the results of this series, we believe that breast surgery should be proposed to patients with occult breast cancer.</br

Analysis of PIK3CA Mutations and Activation Pathways in Triple Negative Breast Cancer.

Triple Negative Breast Cancer (TNBC) accounts for 12-24% of all breast carcinomas, and shows worse prognosis compared to other breast cancer subtypes. Molecular studies demonstrated that TNBCs are a heterogeneous group of tumors with different clinical and pathologic features, prognosis, genetic-molecular alterations and treatment responsivity. The PI3K/AKT is a major pathway involved in the regulation of cell survival and proliferation, and is the most frequently altered pathway in breast cancer, apparently with different biologic impact on specific cancer subtypes. The most common genetic abnormality is represented by PIK3CA gene activating mutations, with an overall frequency of 20-40%. The aims of our study were to investigate PIK3CA gene mutations on a large series of TNBC, to perform a wider analysis on genetic alterations involving PI3K/AKT and BRAF/RAS/MAPK pathways and to correlate the results with clinical-pathologic data.PIK3CA mutation analysis was performed by using cobas® PIK3CA Mutation Test. EGFR, AKT1, BRAF, and KRAS genes were analyzed by sequencing. Immunohistochemistry was carried out to identify PTEN loss and to investigate for PI3K/AKT pathways components.PIK3CA mutations were detected in 23.7% of TNBC, whereas no mutations were identified in EGFR, AKT1, BRAF, and KRAS genes. Moreover, we observed PTEN loss in 11.3% of tumors. Deregulation of PI3K/AKT pathways was revealed by consistent activation of pAKT and p-p44/42 MAPK in all PIK3CA mutated TNBC.Our data shows that PIK3CA mutations and PI3K/AKT pathway activation are common events in TNBC. A deeper investigation on specific TNBC genomic abnormalities might be helpful in order to select patients who would benefit from current targeted therapy strategies

Post-Progression Treatments after Palbociclib plus Endocrine Therapy in HR+/HER2- Metastatic Breast Cancer Patients: What Is the Better Choice?

To date, a consensus has not yet been reached about the therapy sequence after disease progression (PD) on CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer (MBC)

Association between overall survival and clinic-pathological and molecular variables.

<p>OR: Odds Ratio; CI: Confidence Interval</p><p>Association between overall survival and clinic-pathological and molecular variables.</p

Morphologic and immunohistochemical features of Triple Negative Breast Cancer.

<p>(A) Haematoxylin & Eosin stain illustrates a Triple Negative variant with features of high grade invasive ductal carcinoma (original magnification 100X); (B) Immunohistochemistry for EGFR displaying diffuse and moderate membranous and membranous-cytoplasmic immunoreactivity (original magnification 100X); (C) Immunohistochemistry for CK5/6 showing diffuse and intense cytoplasmic immunoreactivity (original magnification 100X); (D) Immunohistochemistry for p- AKT showing diffuse and intense nuclear immunoreactivity (original magnification 100X); (E) Immunohistochemistry for p-p44/42 MAPK displaying diffuse and intense nuclear-cytoplasmic immunoreactivity (original magnification 100X); (F) Immunostaining for PTEN showing diffuse and intense nuclear immunoreactivity (original magnification 100X).</p

Clinic-pathologic and biologic data of the TNBC patients according to mutational status of PIK3CA.

<p>IQR: interquartile range; n: number</p><p>Clinic-pathologic and biologic data of the TNBC patients according to mutational status of PIK3CA.</p

Immunostaining data of the TNBC patients according to mutational status of PIK3CA.

<p>n: number</p><p>*: expressed as immunohistochemical intensity</p><p>§: expressed as H-score</p><p>Immunostaining data of the TNBC patients according to mutational status of PIK3CA.</p

Prognostic impact of KRAS, NRAS, BRAF, and PIK3CA mutations in primary colorectal carcinomas: a population-based study

Activation of oncogenes downstream the EGFR gene contributes to colorectal tumorigenesis and determines the sensitivity to anti-EGFR treatments. The aim of this study was to evaluate the prognostic value of KRAS, BRAF, NRAS and PIK3CA mutations in a large collection of CRC patients from genetically-homogeneous Sardinian population