Histological subtypes in triple negative breast cancer are associated with specific information on survival.

Much research has focused on finding novel prognostic biomarkers for triple negative breast cancer (TNBC), whereas only scattered information about the relation between histopathological features and survival in TNBC is available. This study aims to explore the prognostic value of histological subtypes in TNBC. A multicenter retrospective TNBC cohort was established from five Dutch hospitals. All non-neoadjuvantly treated, stage I-III patients with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 negative breast cancer diagnosed between 2006 and 2014 were included. Clinical and follow-up data (overall survival; OS, relapse free survival; RFS) were retrieved and a central histopathological review was performed. Of 597 patients included (median follow up 62.8 months, median age at diagnosis 56.0 years), 19.4% developed a recurrence. The most prevalent histological subtypes were carcinoma of no special type (NST) (88.4%), metaplastic carcinoma (4.4%) and lobular carcinoma (3.4%). Collectively, tumors of special type were associated with a worse RFS and OS compared to carcinoma NST (RFS HR 1.89; 95% CI 1.18-3.03; p = 0.008; OS HR 1.94; 95% CI 1.28-2.92; p = 0.002). Substantial differences in survival, however, were present between the different histological subtypes. In the presented TNBC cohort, special histological subtype was in general associated with less favorable survival. However, within the group of tumors of special type there were differences in survival between the different subtypes. Accurate histological examination can provide specific prognostic information that may potentially enable more personalized treatment and surveillance regimes for TNBC patients.

Is SLN Biopsy Alone Safe in SLN Positive Breast Cancer Patients?

The Z0011 trial demonstrated no difference in overall survival (OS) and locoregional recurrence in breast cancer patients with a positive sentinel lymph node (SLN) randomized to axillary lymph node dissection (ALND) or no further surgery. The aim of this study was to evaluate locoregional recurrence in a nonrandomized group of SLN positive patients, in whom cALND was not performed, that were retrospectively categorized by the Z0011 eligibility criteria. From two hospital breast cancer databases consisting of 656 consecutive SLN positive breast cancer patients, 88 patients, who did not undergo cALND, were identified. This population was categorized by the Z0011 inclusion criteria (e.g., eligible versus ineligible) and the groups were compared. Thirty-four patients (38.6%) were retrospectively eligible for omitting cALND according to the Z0011 criteria and 54 (61.4%) were not. The median number of SLNs removed in both groups was 1 (range 1-5). The number of positive SLNs did not differ between the groups. Tumor size was slightly larger in the ineligible group (21 mm versus 19 mm) and 76% of patients in the ineligible group underwent a mastectomy. At a median follow-up of 26 months (range 1-84 months), one axillary recurrence was observed in the ineligible group versus 0 in the eligible group. Axillary recurrence was low, even in patients who did not meet the Z0011 inclusion criteria. Future trials that randomize Z0011 ineligible patients are needed to investigate long-term results.

Early presentation of cystic kidneys in a family with a homozygous INVS mutation.

Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is the most frequent monogenic cause of end-stage renal disease in children. Infantile NPHP, often in combination with other features like situs inversus, are commonly caused by mutations in the INVS gene. INVS encodes the ciliary protein inversin, and mutations induce dysfunction of the primary cilia. In this article, we present a family with two severely affected fetuses that were aborted after discovery of grossly enlarged cystic kidneys by ultrasonography before 22 weeks gestation. Exome sequencing showed that the fetuses were homozygous for a previously unreported nonsense mutation, resulting in a truncation in the IQ1 domain of inversin. This mutation induces nonsense-mediated RNA decay, as suggested by a reduced RNA level in fibroblasts derived from the fetus. However, a significant amount of mutant INVS RNA was present in these fibroblasts, yielding mutant inversin protein that was mislocalized. In control fibroblasts, inversin was present in the ciliary axoneme as well as at the basal body, whereas in the fibroblasts from the fetus, inversin could only be detected at the basal body. The phenotype of both fetuses is partly characteristic of infantile NPHP and Potter sequence. We also identified that the fetuses had mild skeletal abnormalities, including shortening and bowing of long bones, which may expand the phenotypic spectrum associated with INVS mutations.