Sentinel Node Biopsy Should Not be Routine in Older Patients with ER-Positive HER2-Negative Breast Cancer Who Are Willing and Able to Take Hormone Therapy

Annals of Surgical Oncology - The SSO Choosing Wisely campaign recommended selective sentinel lymph node biopsy (SLNB) in clinically node-negative women aged ≥ 70 years with ER+ breast...     

An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to anthracyclines or pre-treated with both anthracyclines and taxanes

The aim of this study was to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and potential activity of combined gemcitabine and continuous infusion 5-fluorouracil (5-FU) in metastatic breast cancer (MBC) patients that are resistant to anthracyclines or have been pretreated with both anthracyclines and taxanes. 15 patients with MBC were studied at three European Organization for Research and Treatment of Cancer centres. 13 patients had received both anthracylines and taxanes. Gemcitabine was given intravenously (i.v.) on days 1 and 8, and 5-FU as a continuous i.v. infusion on days 1 through to 14, both drugs given in a 21-day schedule at four different dose levels. Both were given at doses commonly used for the single agents for the last dose level (dose level 4). One of 6 patients at level 4 (gemcitabine 1200 mg/m2 and 5-FU 250 mg/m2/day) had a DLT, a grade 3 stomatitis and skin toxicity. One DLT, a grade 3 transaminase rise and thrombosis, occurred in a patient at level 2 (gemcitabine 1000 mg/m2 and 5-FU 200 mg/m2/day). Thus, the MTD was not reached. One partial response and four disease stabilisations were observed. Only 1 patient withdrew from the treatment due to toxicity. The MTD was not reached in the phase I study. The combination of gemcitabine and 5-FU is well tolerated at doses up to 1200 mg/m2 given on days 1 and 8 and 250 mg/m2/day given on days 1 through to 14, respectively, every 21 days. The clinical benefit rate (responses plus no change of at least 6 months) was 33% with one partial response, suggesting that MBC patients with prior anthracycline and taxane therapy may derive significant benefit from this combination with minimal toxicity.     

Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organization for Research and Treatment of Cancer 10961 Multicenter Phase III Trial.

PURPOSE: To compare the efficacy and tolerability of the combination of doxorubicin and paclitaxel (AT) with a standard doxorubicin and cyclophosphamide (AC) regimen as first-line chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Eligible patients were anthracycline-naive and had bidimensionally measurable metastatic breast cancer. Two hundred seventy-five patients were randomly assigned to be treated with AT (doxorubicin 60 mg/m(2) as an intravenous bolus plus paclitaxel 175 mg/m(2) as a 3-hour infusion) or AC (doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2)) every 3 weeks for a maximum of six cycles. A paclitaxel (200 mg/m(2)) and cyclophosphamide (750 mg/m(2)) dose escalation was planned at cycle 2 if no grade >or= 3 neutropenia occurred in cycle 1. The primary efficacy end point was progression-free survival (PFS). Secondary end points were response rate (RR), safety, overall survival (OS), and quality of life. RESULTS: A median number of six cycles were delivered in the two treatment arms. The relative dose-intensity and delivered cumulative dose of doxorubicin were lower in the AT arm. Dose escalation was only possible in 17% and 20% of the AT and AC patients, respectively. Median PFS was 6 months in the two treatments arms. RR was 58% versus 54%, and median OS was 20.6 versus 20.5 months in the AT and AC arms, respectively. The AT regimen was characterized by a higher incidence of febrile neutropenia, 32% versus 9% in the AC arm. CONCLUSION: No differences in the efficacy study end points were observed between the two treatment arms. Treatment-related toxicity compromised doxorubicin-delivered dose-intensity in the paclitaxel-based regimen     

Irritant potential of dithranol

The minimal irritation dose (MID) for dithranol in 5% salicylic acid vaseline was determined by open patch testing. From the MID, the irritation dose 50 (ID50) was evaluated. It was 0.057% in 100 controls and 0.046% in 100 psoriatic patients, which is not statistically different due to the great differences between individuals. 20 other patients claimed a dithranol hyperreactivity in their history. Only 13 of them, however, showed a decrease in the MID, which was between 0.01 and 0.02% (means = 0.014%), i.e. outside the confidence interval found in the 100 psoriatic patients. 8 of these 13 reacted with blister formation after exposure to 0.1-0.16% dithranol. An allergic contact dermatitis was excluded as the cause of the hyperreactivity. The tolerance to increasing dithranol concentrations after beginning with the MID up to clearance of the lesions, as well as the predominance of granulocytes as compared to lymphocytes in blisters due to dithranol testing, suggest an irritant inflammatory mechanism. In such hyperreactive cases therapy should be started with the MID established in the open patch test.     

Chronic mucocutaneous candida mycosis (CMCC) caused by a T-cell defect

It is reported on a 42-year-old book-keeper with the granulomatous variant of the chronic mucocutaneous candidiasis which could be followed up for 28 years. The intensive systemic treatment with nystatin, 5-fluorocytosin and miconazol combined with the subcutaneous injection of transfer-factor and the local application of ointments containing nystatin and clotrimazol did not only lead to the complete clearing of the lesions (4 years without any relapse), but also to the normalization of the T-lymphocyte count and the reconstitution of the formerly negative delayed type skin reactivity to candidin.     

Using proliferative markers and Oncotype DX in therapeutic decision-making for breast cancer: the B.C. experience

Background

Proliferative scoring of breast tumours can guide treatment recommendations, particularly for estrogen receptor (er)–positive, her2-negative, T1–2, N0 disease. Our objectives were to

• □ estimate the proportion of such patients for whom proliferative indices [mitotic count (mc), Ki-67 immunostain, and Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) recurrence score (rs)] were obtained.
• □ compare the indices preferred by oncologists with the indices available to them.
• □ correlate Nottingham grade (ng) and its subcomponents with Oncotype dx.
• □ assess interobserver variation.

Methods

All of the er-positive, her2-negative, T1–2, N0 breast cancers diagnosed from 2007 to 2011 (n = 5110) were linked to a dataset of all provincial breast cancers with a rs. A 5% random sample of the 5110 cancers was reviewed to estimate the proportion that had a mc, Ki-67 index, and rs. Correlation coefficients were calculated for the rs with ng subcomponent scores. Interobserver variation in histologic grading between outside and central review pathology reports was assessed using a weighted kappa test.

Results

During 2007–2011, most cancers were histologically graded and assigned a mc; few had a Ki-67 index or rs. The ng and mc were significantly positively correlated with rs. The level of agreement in histologic scoring between outside and central pathology reports was good or very good. Very few cases with a low mc had a high rs (1.8%).

Conclusions

Patients with low ng and mc scores are unlikely to have a high rs, and thus are less likely to benefit from chemotherapy. In the context of limited resources, that finding can guide clinicians about when a rs adds the most value.