Michael J. Byrne

The importance of the histologic grade of invasive breast carcinoma and response to chemotherapy

Histologic grade is well recognized for its prognostic significance in cases of primary operable invasive breast carcinoma; however, the majority of studies in which grade has been assessed have been based on single‐center trials. In addition, the role of grade in predicting response to chemotherapy has not been examined in many previous studies.

Decreased immunoreactivity for p27 protein in patients with early-stage breast carcinoma is correlated with HER-2/neu overexpression and with benefit from one course of perioperative chemotherapy in patients with negative lymph node status: results from International Breast Cancer Study Group Trial V.

The objective of this study was to clarify the prognostic and predictive value of immunoreactivity for the cyclin‐dependent kinase inhibitor p27(Kip1) in patients with early‐stage breast carcinoma and to investigate its relation with clinicopathologic features and other markers.

People's perceptions of cancer survivability: implications for oncologists

Individuals typically overestimate survival for lung cancer and underestimate it for melanoma. However, reporting of results generally masks the extent of disagreement between people on survival rates. Most methods used to question individuals are of little use and are not comparable across studies. The topic of peoples perceptions of survival for various cancers is under-researched. A clearer definition is needed of survivability, as is a standard way to measure it and then present the information. We have undertaken a review of studies reporting public perceptions of cancer survival rates and compared the results, where possible, with actual survival rates. We also investigate some potential implications of peoples underestimation or overestimation of survival for screening and prevention behaviours and delineate implications for oncologists.

Possible infectious etiology of six cases of Ewing's sarcoma in Western Australia.

Six cases of Ewings sarcoma occurring in Western Australia during a 2‐year period are reported. All six patients lived in rural habitats and reported exposure to farm animals. There was evidence of direct contact between two patients over a 3‐year period preceding the diagnosis of their tumors. These features raise the possibility that Ewings sarcoma has an infectious etiology.

Cyclophosphamide, vincristine and procarbazine in the treatment of malignant melanoma.

Patients with advanced malignant melanoma were randomly assigned to treatment with cyclophosphamide and vincristine (CV) or cyclophosphamide, vincristine, and procarbazine (CVP). The objective response rates to each regimen (CV 30%, CVP 33%) were the same. Patients with disease confined to skin, subcutaneous tissue nodes, lung, or pleura had a significantly superior response rate to that in those with disease involving liver, bone or brain. The survival of responders was superior to that of nonresponders. The efficacy and moderate toxicity of CV suggests that further work with this combination in malignant melanoma is indicated.

Anemia during adjuvant non-taxane chemotherapy for early breast cancer: Incidence and risk factors from two trials of the International Breast Cancer Study Group

Goal of the workAnemia is a common side effect of chemotherapy. Limited information exists about its incidence and risk factors. The objective of this study was to evaluate the incidence of anemia and risk factors for anemia occurrence in patients with early breast cancer who received adjuvant chemotherapy.Materials and methodsWe evaluated risk factors for anemia in pre- and post/perimenopausal patients with lymph node-positive early breast cancer treated with adjuvant chemotherapy in two randomized trials. All patients received four cycles of doxorubicin and cyclophosphamide (AC) followed by three cycles of cyclophosphamide, methotrexate, fluorouracil (CMF). Anemia incidence was related to baseline risk factors. Multivariable analysis used logistic and Cox regression.Main resultsAmong the 2,215 available patients, anemia was recorded in 11% during adjuvant chemotherapy. Grade 2 and 3 anemia occurred in 4 and 1% of patients, respectively. Pretreatment hemoglobin and white blood cells (WBC) were significant predictors of anemia. Adjusted odds ratios (logistic regression) comparing highest versus lowest quartiles were 0.18 (P < 0.0001) for hemoglobin and 0.52 (P = 0.0045) for WBC. Age, surgery type, platelets, body mass index, and length of time from surgery to chemotherapy were not significant predictors. Cox regression results looking at time to anemia were similar.ConclusionsModerate or severe anemia is rare among patients treated with AC followed by CMF. Low baseline hemoglobin and WBC are associated with a higher risk of anemia.

Breast cancer in Western Australia in 1989: IV. summary of histopathological assessment in 655 cases

&NA; This study was part of a population‐based survey of all cases of breast cancer diagnosed in Western Australia in 1989. The paper concerns histopathology reporting by pathologists in 655 cases of carcinoma of the breast in that year, before the introduction of mammographic screening programmes. Pathological features of the neoplasms are documented, and the extent to which information known to be of clinical or prognostic importance was included in the reports is analysed. 96.5% of all pathology reports included information on breast cancer subtype and, in 98.6% of cases with axillary dissection, the number of lymph nodes dissected, and the number containing metastatic tumor was stated. In 83.7% of cases of invasive carcinoma exact tumor dimensions were recorded. In 44.9% of cases histological grade was recorded, and information about excision margins was present in 60% of reports overall. The reporting of pathological features in many instances was limited by the way in which the specimen was handled prior to reception. At the time of the study, views about the importance of many aspects of histological assessment were still evolving. Even now, for example, consensus is still being reached on the value of histological grading in predicting prognosis and whether reliable histological assessment of such factors as extent of DCIS and completeness of excision of DCIS is possible. The introduction of mammographic screening since 1989 has provided a focus for wider discussion about the value of histological information in prognostication and patient management. A case is made to support the use of “check lists” for surgical pathology reports in cases of breast cancer.

Trade-offs in quality of life and survival with chemotherapy for advanced breast cancer: mature results of a randomized trial comparing single-agent mitoxantrone with combination cyclophosphamide, methotrexate, 5-fluorouracil and prednisone

BackgroundWe evaluate trade-offs between quality of life (QoL) and survival improvement for two chemotherapy regimens in advanced breast cancer. We also report on the long-term survival of patients in the ANZ 8614 clinical trial.MethodsA total of 391 patients were randomized to mitoxantrone (14 mg/m2 intravenously every 21 days) or a combination of cyclophosphamide 100 mg/m2 and prednisone 40 mg/m2 orally days 1 to 14 plus methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 intravenously days 1 and 8 every 28 days (CMFP). QoL was self-assessed on 14 linear analog scales. We computed the mean differences between the two treatments as products of the mean differences in global QoL, progression-free survival and overall survival.ResultsCMFP led to a higher overall tumor response (39% vs. 25%, P=0.004) and longer progression-free survival (PFS) (median 5.6 vs 3.9 months, P=0.02) but with significantly more toxicity from alopecia, mucositis, diarrhea, anemia and lethargy. Overall survival (OS) was similar in the two groups (median 10.1 vs 11.6 months, P=0.81). QoL over the first 12 weeks was rated better by patients on CMFP for mood (P=0.04), nausea and vomiting (P=0.01), and feeling sick (P=0.02) but worse for hair loss (P<0.0001). A weighted combination of individual QoL items favoured CMFP (subset score mean difference 2.4, P=0.03). A global QoL score tended to favour CMFP (global score mean difference 1.7, P=0.18). Quality-adjusted PFS was significantly longer with CMFP (mean 7.208 vs 5.965 months, P=0.04), but quality-adjusted OS was not significantly different (mean 11.832 vs 11.315 months, P=0.57).ConclusionDespite the greater toxicity, the superior antitumor activity of CMFP led to an overall improvement in quality-adjusted PFS. In advanced breast cancer, in clinical decision making about treatment for palliative intent, the principle used to assess trade-offs between antitumor efficacy and toxicity remains relevant and applicable to all modern therapeutic agents.

Dose Intensity and Outcome with Combination Chemotherapy for Germ-Cell Carcinoma

Two hundred and fifty-three patients with advanced stage germ cell carcinoma received induction chemotherapy with vinblastine, bleomycin and cisplatin, sometimes with subsequent surgical resection of residual masses. Overall, 191 patients (76%) achieved complete remission or no evidence of disease after surgery (CR + NED). With 64 months median follow-up only 24 patients have relapsed (13%) and 68% of all patients treated are long-term survivors and 84% of patients entering CR + NED are alive. Toxicity with this chemotherapy was considerable, including seven deaths from leukopenia and septicaemia and eight deaths from bleomycin lung toxicity. Dose reductions or omissions of the drug from the treatment programme was necessary with cisplatin in 8% of patients, with vinblastine in 37% and with bleomycin in 35% of patients. Analysis of these alterations in dose intensity for each drug revealed that initial treatment response and subsequent survival were not compromised by reductions in intended doses of drug administered for either vinblastine or bleomycin. Too few patients had dose reductions of cisplatin for meaningful analysis. This apparent lack of major dose-response effect for either vinblastine or bleomycin in the present treatment programme for germ cell carcinoma has prompted the initiation of a randomized study to determine whether deletion of bleomycin from treatment for patients with good prognostic pretreatment characteristics improves the therapeutic index of this very successful therapy.

Immunological effects of cancer chemotherapy in malignant melanoma

SummaryThe effects on the immune system of highdose cyclical combination chemotherapy were studied in nine patients with advanced malignant melanoma. Chemotherapy consisted of monthly cycles of dimethyl triazeno imidazole carboxamide 150 mg/m2 i.v. daily from days 1–5, cyclophosphamide 1000 mg/m2 i.v. on day 5, and vincristine 1.4 mg/m2 i.v. on day 5.Immunological testing was carried out prior to treatment and at weekly intervals during the first month.B, T and non-B, non-T cell numbers all tended to fall early in the cycle as did the phytohaemagglutinin(PHA)-induced transformation and PHA-induced cytotoxicity to chicken red cells. Although PHA-induced transformation and cytotoxicity usually returned to normal by day 29, B and T cell numbers often remained subnormal. In contrast, levels for antibody-dependent, cell-mediated cytotoxicity (ADCC) were relatively stable throughout the cycle. Two patients with subsequent tumour response to therapy had rebound supranormal PHA transformations between weeks 1 and 3 of the first cycle. No other changes correlated with prognosis in individual patients.Analysis of the temporal relationships between PHA transformation, PHA-induced cytotoxicity, and ADCC supported the concept that the three assays reflect the function of separate mononuclear cell subpopulations.The stability of ADCC is of particular interest in view of other work suggesting that this function may be important in immune responses to tumours, including melanoma.