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

/pdf/reversed-greenhouse-temperatures-alter-carbohydrate-status-2vhy222rm3.pdf

Reversed greenhouse temperatures alter carbohydrate status in Lilium longiflorum Thunb. 'Nellie White'

Preharvest aminoethoxyvinylglycine (AVG) and 1-methylcyclopropene (1-MCP) effects on ethylene and starch concentrations of ‘Empire’ and ‘McIntosh’ apples

Irradiation of FeDTPA-containing nutrient solutions by a fluorescent plus incandescent light source resulted in the loss of both Fe-chelate and soluble Fe, the formation of a precipitate that was composed mostly of Fe, and a rise in pH. The rate of Fe-chelate photodegradation in solution increased with irradiance intensity and with solution temperature under irradiation, but irradiance had the greater effect. Fe-chelates absorb in the blue and UV regions of the spectrum. Removal of these wavelengths with a spectral filter eliminated photodegradation. Chemical name used: ferric diethylenetriaminepentaacetic acid (FeDTPA).

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Photodegradation of FeDTPA in Nutrient Solutions. I. Effects of Irradiance, Wavelength, and Temperature

Several experiments were conducted to find effective ways of utilizing gibberellin 4+7 (GA 4+7 ) and benzyladenine (BA) to prevent leaf chlorosis during greenhouse production of Easter lilies (Lilium longiflorum Thunb.) while minimizing the undesirable side effects on stem elongation. On an absolute concentration basis, GA 4+7 was much more effective than BA in preventing leaf chlorosis. Excessive levels of GA 4+7 , however, tended to cause stem elongation. When applied at around the visible bud stage, if the foliage was well covered with the spray solution, 25 mg.L -1 of GA 4+7 was adequate for maximum protection against leaf chlorosis. Increasing the GA 4+7 concentration above 25 mg.L -1 gave no additional benefit on leaf chlorosis. Two possible modes of GA 4+7 uptake during a foliar spray application (absorption through leaves and stems, and root uptake of the extra run-off) were studied in terms of their relative contribution to leaf chlorosis and stem elongation. Although both modes of uptake prevented leaf chlorosis, foliar uptake was much more effective than root uptake. However, GA 4+7 taken up by the roots contributed mainly to stem elongation. When sprayed to leaves on only the lower half of the plant, a 10-mL spray of either 25 or 50 mg.L -1 of each GA 4+7 and BA was enough for complete protection against leaf chlorosis. Increasing volumes had no additional benefit on leaf chlorosis, but increased the chances of unwanted stem elongation.

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Minimizing Stem Elongation During Spray Applications of Gibberellin4+7 and Benzyladenine to Prevent Leaf Chlorosis in Easter Lilies

Additional index words. cytokinin, flower longevity, Lilium longiflorum, postharvest physiology, senescence Abstract. The effects of Promalin® (PROM; 100 mg·L -1 each of GA4+7 and benzyladenine (BA)) sprays on leaf chlorosis and plant height during greenhouse production of ancymidol- treated (two 0.5-mg drenches per plant) Easter lilies ( Lilium longiflorum Thunb. 'Nellie White') were investigated. Spraying with PROM at early stages of growth (36 or 55 days after planting (DAP)) completely prevented leaf chlorosis until the puffy bud stage, and plants developed less severe postharvest leaf chlorosis after cold storage at 4 °C for 2 weeks. When PROM was sprayed on plants in which leaf chlorosis had already begun (80 DAP), further leaf chlorosis was prevented during the remaining greenhouse phase and during the postharvest phase. PROM caused significant stem elongation (23% to 52% taller than controls) when applied 36 or 55 DAP, but not when applied at 80 DAP or later. The development of flower buds was not affected by PROM treatments. Although PROM sprays applied at 55 DAP or later increased postharvest flower longevity, earlier applica- tions did not. Chemical names used: N-(phenylmethyl)-1H-purine 6-amine (benzyladenine, BA); α-cyclopropyl-α-(p-methoxyphenyl)-5-pyrimidinemethanol (ancymidol).

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William B. Miller

Papers

Reversed greenhouse temperatures alter carbohydrate status in Lilium longiflorum Thunb. 'Nellie White'

Preharvest aminoethoxyvinylglycine (AVG) and 1-methylcyclopropene (1-MCP) effects on ethylene and starch concentrations of ‘Empire’ and ‘McIntosh’ apples

Photodegradation of FeDTPA in Nutrient Solutions. I. Effects of Irradiance, Wavelength, and Temperature

Minimizing Stem Elongation During Spray Applications of Gibberellin4+7 and Benzyladenine to Prevent Leaf Chlorosis in Easter Lilies

Timing of Gibberellin4+7 + Benzyladenine Sprays Influences Efficacy against Foliar Chlorosis and Plant Height in Easter Lily