Response to dual HER2 blockade in a patient with HER3-mutant metastatic breast cancer.

BACKGROUND: HER3 activating mutations have been shown in preclinical models to be oncogenic and ligand-independent, but to depend on kinase-active HER2. PATIENTS AND METHODS: Whole-exome sequencing of the primary HER2-negative breast cancer and its HER2-negative synchronous liver metastasis from a 46-year-old female revealed the presence of an activating and clonal HER3 G284R mutation. RESULTS: HER2 dual blockade with trastuzumab and lapatinib as third-line therapy led to complete metabolic response in 2 weeks and confirmed radiological partial response after 8 weeks. Following the resection of the liver metastasis, the patient remains disease-free 40 weeks after initiation of the HER2 dual blockade therapy. Immunohistochemical analysis demonstrated a substantial reduction of phospho-rpS6 and phospho-AKT in the post-therapy biopsy of the liver metastasis. DISCUSSION: This is the first-in-man evidence that anti-HER2 therapies are likely effective in breast cancers harboring HER3 activating mutations.

Mathematical relationships between uterine contractions, cervical dilatation, descent and rotation in spontaneous vertex deliveries.

OBJECTIVE: To determine the mathematical relationships between the strength and duration of the uterine contractions, the descent and rotation of the fetal head and the degree of cervical dilatation in 50 multiparous women with spontaneous vaginal deliveries using a simple device applied to the fetal vertex. METHOD: A simple device for monitoring the progress of labor was applied to the fetal vertex. The device allows the continuous monitoring of descent and rotation of the fetal head. The amount of descent and the degree of rotation were also determined by repeated vaginal examinations as well as the degree of cervical dilatation. The frequency of uterine contractions was also recorded on a partogram. RESULT: A good correlation was found between the amount of descent of the fetal vertex (r = 0.975) and between the degree of rotation of the fetal head (0.83) determined by both methods. Multiple regression analysis was then performed and the degree of cervical dilatation in cm at any given time during the first stage of labor was found to be equal to 2.859 + 0.583 fetal head station in (cm) + 0.1983 internal rotation in degrees -0.0493 (station x internal rotation) + 0.1599 station2 + 0.3622 uterine contractions per 10 min. A nomogram was constructed allowing the calculation of cervical dilatation for a given station of the head, degree of rotation and frequency of uterine contractions. CONCLUSION: There is a defined mathematical relationship between the degree of descent and rotation of the fetal head, the degree of cervical dilatation and the frequency of uterine contractions in multiparous women with vertex presentation. The first three variables can be continuously determined by using the described device. Incorporation of the device into a reusable fetal scalp electrode allows the dual mechanical and electronic monitoring during labor with minimal vaginal examinations.

[Does molecular biology play any role in ductal carcinoma in situ?]. / Carcinomes canalaires in situ du sein : rôle potentiel de la biologie moléculaire.

The natural history of ductal carcinoma in situ (DCIS) is not fully elucidated, but it is recognized that DCIS is the true precursor of invasive carcinoma. Studies could show that DCIS is as heterogeneous as invasive ductal carcinoma, yet, they were unable to predict which DCIS will progress to invasion. Several biomarkers were also demonstrated to have a certain prognostic value. However, except for estrogen receptors and HER2, biomarkers are not yet widely used in clinical practice since their predictive value has not proven to be better than the grade and the classical classifying systems of DCIS. Identifying biomarkers for risk of invasiveness in DCIS could be of great value to help high risk patients through the management of their disease and to avoid overtreatment in low risk patients.

Clear margins for invasive lobular carcinoma: a surgical challenge.

BACKGROUND: The main goal of breast conservative surgery (BCS) is the complete removal of cancer with clear margins and no deformity of the breast. However, in invasive lobular carcinoma (ILC) this goal is hard to achieve because of the underestimation of tumor size. Our study was the first to show the role of surgical techniques in the achievement of clear margins for ILC. METHODS: We reviewed 73 patients with ILC who underwent BCS at Paris Breast Center between January 2005 and June 2008. Full thickness excision (FTE) was performed in a routine basis and oncoplastic surgery (OPS) upon tumor location, volume ratio and overall density of the breast. Margin status was evaluated as positive, close or clear. RESULTS: Positive/close margins were found in 39% of cases and were lower than what was described in the literature (49-63%). FTE was performed in 47 (64%) patients and OPS in 26 (36%) patients. No positive/close margins were observed in patients with lesions located in the lower/central quadrants. Multivariate analysis showed multifocality, larger tumor size and FTE to be independent risk factors for positive margins at final surgery. CONCLUSIONS: Our rate of positive/close margins for ILC was lower than what was described in the literature. The determinant key difference was in our surgical procedures with FTE or OPS differing from the standard BCS described in the literature and we suggest that OPS is to be considered for ILC. It allows larger breast conservative surgery with good cosmetic results and lower rate of compromised margins.