J. Appl. Cryst.の発刊に際して

Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011

Purpose The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain. Methods Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane–based chemotherapy in seven randomized trials were analyzed. Results Disease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes ...

https://ascopubs.org/doi/pdf/10.1200/JCO.2011.38.8595

Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes

Summary Background Studies with pertuzumab, a novel anti-HER2 antibody, show improved efficacy when combined with the established HER2-directed antibody trastuzumab in breast cancer therapy. We investigated the combination of pertuzumab or trastuzumab, or both, with docetaxel and the combination of pertuzumab and trastuzumab without chemotherapy in the neoadjuvant setting. Methods In this multicentre, open-label, phase 2 study, treatment-naive women with HER2-positive breast cancer were randomly assigned (1:1:1:1) centrally and stratified by operable, locally advanced, and inflammatory breast cancer, and by hormone receptor expression to receive four neoadjuvant cycles of: trastuzumab (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) plus docetaxel (75 mg/m 2 , escalating, if tolerated, to 100 mg/m 2 every 3 weeks; group A) or pertuzumab (loading dose 840 mg, followed by 420 mg every 3 weeks) and trastuzumab plus docetaxel (group B) or pertuzumab and trastuzumab (group C) or pertuzumab plus docetaxel (group D). The primary endpoint, examined in the intention-to-treat population, was pathological complete response in the breast. Neither patients nor investigators were masked to treatment. This study is registered with ClinicalTrials.gov, number NCT00545688. Findings Of 417 eligible patients, 107 were randomly assigned to group A, 107 to group B, 107 to group C, and 96 to group D. Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate (49 of 107 patients; 45·8% [95% CI 36·1–55·7]) compared with those given trastuzumab plus docetaxel (group A; 31 of 107; 29·0% [20·6–38·5]; p=0·0141). 23 of 96 (24·0% [15·8–33·7]) women given pertuzumab plus docetaxel (group D) had a pathological complete response, as did 18 of 107 (16·8% [10·3–25·3]) given pertuzumab and trastuzumab (group C). The most common adverse events of grade 3 or higher were neutropenia (61 of 107 women in group A, 48 of 107 in group B, one of 108 in group C, and 52 of 94 in group D), febrile neutropenia (eight, nine, none, and seven, respectively), and leucopenia (13, five, none, and seven, respectively). The number of serious adverse events was similar in groups A, B, and D (15–20 serious adverse events per group in 10–17% of patients) but lower in group C (four serious adverse events in 4% of patients). Interpretation Patients given pertuzumab and trastuzumab plus docetaxel (group B) had a significantly improved pathological complete response rate compared with those given trastuzumab plus docetaxel, without substantial differences in tolerability. Pertuzumab and trastuzumab without chemotherapy eradicated tumours in a proportion of women and showed a favourable safety profile. These findings justify further exploration in adjuvant trials and support the neoadjuvant approach for accelerating drug assessment in early breast cancer. Funding F Hoffmann-La Roche.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(11)70336-9.pdf

Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial

Purpose To measure residual disease after neoadjuvant chemotherapy in order to improve the prognostic information that can be obtained from evaluating pathologic response. Patients and Methods Pathologic slides and reports were reviewed from 382 patients in two different treatment cohorts: sequential paclitaxel (T) then fluorouracil, doxorubicin, and cyclophosphamide (FAC) in 241 patients; and a single regimen of FAC in 141 patients. Residual cancer burden (RCB) was calculated as a continuous index combining pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses. Results RCB was independently prognostic in a multivariate model that included age, pretreatment clinical stage, hormone receptor status, hormone therapy, and pathologic response (pathologic complete response [pCR] v residual disease [RD]; hazard ratio 2.50; 95% CI 1.70 to 3.69; P .001). Minimal RD (RCB-I) in 17% of patients carried the same prognosis as pCR (RCB-0). Extensive RD (RCB-III) in 13% of patients was associated with poor prognosis, regardless of hormone receptor status, adjuvant hormone therapy, or pathologic American Joint Committee on Cancer stage of residual disease. The generalizability of RCB for prognosis of distant relapse was confirmed in the FAC-treated validation cohort. Conclusion RCB determined from routine pathologic materials represented the distribution of RD, was a significant predictor of DRFS, and can be used to define categories of near-complete response and chemotherapy resistance. J Clin Oncol 25:4414-4422. © 2007 by American Society of Clinical Oncology

https://ascopubs.org/doi/pdf/10.1200/JCO.2007.10.6823

Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy

Comparison of the dynamics of non-structural carbohydrate pools in cut tulip stems supplied with sucrose or trehalose

N.m.r. characterization of trehalulose from the excrement of the sweet potato whitefly, Bemisia tabaci

-1 at 28 DPP. Reducing sugars accounted for 84% of the inflorescence TSC at 4 DPP, dropping to 48% at 28 DPP. Fructan concentration decreased through 16 DPP and then remained unchanged, while starch levels rose from 25 to 34 mg·g - 1 dry weight through 12 DPP, then decreased. Fractans decreased in polymer- ization during petal expansion. This result suggests an alternate use of fructans and starch as pools of available reserve -. . . carbohydrate during petal expansion in chrysanthemum. Many studies have dealt with factors that influence the lon- gevity of cut flowers (Halevy and Mayak, 1979), whereas little information is available regarding longevity of flowering pot plants. Preharvest factors, such as nutrient status, and cultivar selection have been shown to affect plant longevity in potted poinsettia (Scott et al., 1982) and chrysanthemum (Nell, 1989). Easter lilies grown under suboptimal irradiances have low leaf and flower bud carbohydrate levels and their flower longevity may be affected (Miller and Langhans, 1989). In chrysanthe- mum, Nell et al. (1990) found that postproduction longevity is reduced when low irradiance levels are used during production. These results suggest that carbohydrate levels may play a role in the longevity of potted chrysanthemums. With cut flowers, an important aspect of increasing longevity is maintenance of the carbohydrate pool and active osmotica in floral tissues (Mayak and Halevy, 1980). This phenomenon is demonstrated by the delay in senescence achieved by adding sugar to cut-flower vase solutions. A detailed investigation of the carbohydrate metabolism of whole chrysanthemum plants has not yet been made. The objectives of this study were to characterize the relationship between carbohydrate levels and flower senescence in chrysanthemum in florescences and de- scribe the changes in carbohydrate pool sizes in whole plants during senescence.

/pdf/postproduction-carbohydrate-levels-in-pot-chrysanthemums-3c2pmz80sh.pdf

Postproduction Carbohydrate Levels in Pot Chrysanthemums

Stickiness of cotton fiber is usually caused by honeydew deposits from phloem- feeding insects, including whiteflies and aphids. This work was conducted to determine if the specific sugars commonly...

Stickiness Potential of Individual Insect Honeydew Carbohydrates on Cotton Lint

Three invertase forms (EC 3.2.1.26) were identified in soluble extracts from developing flower buds of Lilium longiflorum Thunb. cv. Nellie White. The enzymes were separable on a diethylaminoethyl (DEAE)-Sephacel column and designated invertase I. II or III according to the order of elution from Sephacel. To determine tissue specificity of these floral invertases, anthers were separated from tepal. pistil and filament tissue, and analyzed for invertase activity. Invertase I was localized primarily in anthers, with invertases II and III being present in much smaller amounts (less than 5% of the invertase I activity). Much higher levels of invertases II and III were found in the nonanther organs of the flower, where essentially no invertase 1 was detectable. Further purification of each form (using gel filtration. Con-A-Sepharose affinity chromatog-raphy and hydrophobic interaction chromatography on phenyl-agarose) resulted in 135- 189- and 202-fold purification of pooled fractions from DEAE-Sephacel. respectively, and established that each invertase form is a glycoprotein. Each was an acid invertase. with pH optima between 4.0 and 5.0 and an apparent molecular mass of 77 500 Da (as determined by Sephadex gel filtration). The invertases had sucrose Km values of 1.0. 6.4 and 6.6 mM. and temperature optima of 40. 50 and 45°C. respectively. A temperature stability study revealed that invertase III was the most thermostable, followed by II and I. Invertases II and III had lower affinity to raffinose and stachyose than invertase I. All three enzymes were completely inhibited by Hg2+ or Ag+ ions at 1.7 mM. At this concentration. Cu2-showed differential partial inhibition. Although fructan was shown to be present in both anther and nonanther tissues of Lilium flower buds, these invertases showed no sucrose:sucrose fructosyltransferase (EC 2.4.1.99) activity.

William B. Miller

Papers

Comparison of the dynamics of non-structural carbohydrate pools in cut tulip stems supplied with sucrose or trehalose

N.m.r. characterization of trehalulose from the excrement of the sweet potato whitefly, Bemisia tabaci

Postproduction Carbohydrate Levels in Pot Chrysanthemums

Stickiness Potential of Individual Insect Honeydew Carbohydrates on Cotton Lint

Characterization and localization of three soluble invertase forms from Lilium longiflorum flower buds