ABSTRACT:Most known interactions between herbal extracts and drugs involve the inhibition of drug-metabolizing enzymes, but little is yet known about the possible role of transporters in these interactions. In this study, we have examined the effects of herbal extracts used in dietary supplements on the function of organic aniontransporting polypeptide B (OATP-B; OATP2B1), which is expressed on human intestinal epithelial cells and is considered to be involved in the intestinal absorption of various drugs. Specifically, the effects of 15 herbal extracts on uptake of estrone-3-sulfate, a typical OATP-B substrate, by human embryonic kidney 293 cells stably expressing OATP-B were evaluated. At concentration levels considered likely to be attainable in the human intestine, extracts of bilberry, echinacea, green tea, banaba, grape seed, ginkgo, and soybean potently inhibited estrone-3-sulfate uptake by 75.5, 55.5, 82.1, 61.1, 64.5, 85.4, and 66.8%, respectively (P < 0.01). The inhibitory effect of ginkgo leaf extract was concentration-dependent (IC 50 ‫؍‬ 11.2 ؎ 3.3 g/ml) and reversible. Moreover, flavonol glycosides and catechins significantly inhibited the function of OATP-B, suggesting that the inhibitory effects of the herbal extracts on OATP-B may be primarily attributable to flavonoids. The extracts of mulberry, black cohosh, and Siberian ginseng moderately (but significantly) inhibited estrone-3-sulfate uptake by 39.1, 47.2, and 49.2%, respectively (P < 0.05). Extracts of barley, Job's tears, rutin, rafuma, and passionflower were ineffective. These results suggest that coadministration of some dietary supplements may decrease the absorption of orally administered substrates of OATP-B.

PurposeBreast conserving surgery (BCS) followed by whole breast irradiation (WBI) is the standard of care for breast cancer patients. However, there is a risk of coronary events with WBI therapy. In this study, we compared the radiation dose in the left anterior descending artery (LAD) in patients receiving partial breast irradiation (PBI) with WBI.Material and methodsWe evaluated consecutive patients who underwent adjuvant radiotherapy after BCS between October 2008 and July 2014. Whole breast irradiation patients received 50 Gy in fractions of 2 Gy to the entire breast. Partial breast irradiation was performed using multicatheter brachytherapy at a dose of 32 Gy in eight fractions. The mean and maximal cumulative doses to LAD were calculated. The radiotherapeutic biologically effective dose of PBI was adjusted to WBI, and radiation techniques were compared.ResultsOf 379 consecutive patients with 383 lesions receiving radiotherapy (151 WBI and 232 PBI lesions), 82 WBI and 100 PBI patients were analyzed. In WBI patients, the mean and maximal cumulative doses for left-sided breast cancer (2.13 ± 0.11 and 8.19 ± 1.21 Gy, respectively) were significantly higher than those for right-sided (0.37 ± 0.02 and 0.56 ± 0.03 Gy, respectively; p < 0.0001). In PBI patients with left-sided breast cancer, the doses for tumors in inner quadrants or central location (2.54 ± 0.21 and 4.43 ± 0.38 Gy, respectively) were significantly elevated compared to outer quadrants (1.02 ± 0.17 and 2.10 ± 0.29 Gy, respectively; p < 0.0001). After the adjustment, the doses in PBI patients were significantly reduced in patients with tumors only in outer quadrants (1.12 ± 0.20 and 2.43 ± 0.37 Gy, respectively; p = 0.0001).ConclusionsTumor control and dose to LAD should be considered during treatment since PBI may reduce the risk of coronary artery disease especially in patients with lateral tumors in the left breast.

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Purpose: In partial-breast irradiation (PBI), accurate lumpectomy cavity (LC) delineation is critical. Seroma-based delineation (SBD) using computed tomography (CT) with clips remains uncertain, causing an expansion of the LC and planning target volume (PTV). In catheter-based delineation (CBD), the implanted catheters were used as reference markers for LC delineation in multicatheter interstitial brachytherapy (MIB). Material and methods: Between October 2008 and October 2018, 513 patients who underwent MIB-PBI were examined. In CBD, anatomical relations of LC to catheters were recorded. In randomly selected 22 CBD cases, the LC volume and PTV were retrospectively recontoured on SBD, and the relationship between the contribution of CBD and cavity visuality was evaluated. The LC volume and PTV before and after the introduction of CBD were compared. Results: The mean LC volumes based on SBD and CBD were 19.1 cm 3 and 14.1 cm 3 , respectively (p < 0.001). The mean PTVs based on SBD and CBD were 47.9 cm 3 and 35.7 cm 3 , respectively (p < 0.0001). More reductions in the LC volume (5.1 cm 3) (p < 0.05) and PTV (7.7 cm 3) (p = 0.13) were observed in the poorly visible LC than in the visible LC. The LC volume and PTV before the introduction of CBD (n = 411) were compared with those after introduction (n = 102). Significant reductions were observed in the LC volume (5.9 cm 3) (p < 0.0001) after the introduction of CBD; moreover, PTV tended to be reduced (3.9 cm 3) (p = 0.17). Conclusions: CBD may help to establish the standardized procedure for MIB-PBI and prevent unnecessary radiation exposure to the normal breast tissue.

Background: This retrospective study aimed to evaluate the efficacy of a 3.6-mg dose of pegfilgrastim for primary prophylaxis in Japanese breast cancer patients receiving dose-dense chemotherapy. Methods: Patients treated with adjuvant or neoadjuvant chemotherapy for early-stage breast cancer at the Tokyo-West Tokushukai Hospital were included in this analysis. Because 6 mg pegfilgrastim has not yet been approved for use in Japan, we compared the outcomes of a dose-dense doxorubicin and cyclophosphamide regimen plus 3.6 mg pegfilgrastim support with a conventional dose epirubicin and cyclophosphamide regimen. The incidence of febrile neutropenia, relative dose intensity, dose delay, dose reduction, regimen change and hospitalization because of neutropenia were assessed. Results: From November 2013 to March 2016, 97 patients with stage I-III invasive breast cancer were analyzed (dose-dense doxorubicin and cyclophosphamide plus 3.6-mg pegfilgrastim group, n = 41; epirubicin and cyclophosphamide group, n = 56; median ages, 49.0 and 48.5 years, respectively). Febrile neutropenia occurred during the first chemotherapy cycle in 7 of 56 patients (12.5%) in the epirubicin and cyclophosphamide group and 0 of 41 patients in the dose-dense doxorubicin and cyclophosphamide group (P = 0.02). The average relative dose intensities were 97.9% and 96.8%, respectively (P = 0.28), with corresponding dose delay rates of 4.9% (2/41) and 16.1% (9/56), respectively (P = 0.11) and dose reduction rates of 0% (0/41) and 7.1% (4/56), respectively (P = 0.16). Conclusions: Our results indicate the efficacy of a 3.6-mg pegfilgrastim dose for the primary prevention of febrile neutropenia in dose-dense doxorubicin-and cyclophosphamide-treated Japanese breast cancer patients.