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Biomedical subjects

A Goldhirsch

Publications and source records attributed to A Goldhirsch.

At least 217 records · Page 12Linked to original sources
PubMed1990

The magnitude of endocrine effects of adjuvant chemotherapy for premenopausal breast cancer patients. The International Breast Cancer Study Group.

We analysed the incidence of amenorrhoea and its association with outcome in a cohort of 1127 premenopausal women with breast cancer randomized to International Trial V (formerly Ludwig V). For 552 patients without axillary lymph node involvement, one course of perioperative cytotoxic drugs was compared with no-adjuvant chemotherapy. For 575 patients with node-positive disease, a single course of cytotoxic chemotherapy was compared with a prolonged treatment (6 or 7 courses). Amenorrhoea was defined as having no menstrual bleeding for a 3-month interval within the first 9 months after surgery. Amenorrhoea was observed in 21% of the 199 patients with node-negative breast cancer who received no adjuvant therapy, 31% of the 353 node-negative patients who had a single course of cytotoxic therapy, 31% of the 188 patients with node-positive disease who had the same short-duration therapy, and 68% of the 387 node-positive patients who had a prolonged adjuvant therapy. Amenorrhoea was associated with an increased disease-free survival (DFS) only in the patients with prolonged cytotoxic therapy: 4-year DFS % (+/- s.e.) was 68% +/- 3% vs. 61% +/- 5% for the amenorrhoea and the no-amenorrhoea groups, respectively, (p = 0.05). In contrast, the comparison between prolonged therapy and one single course among node-positive patients showed a much larger treatment effect (4-year DFS 66% vs. 38%, p less than 0.0001). We conclude that although cytotoxics-induced amenorrhoea is associated with a better outcome, it is unlikely that this form of endocrine manipulation is the main mechanism of response to adjuvant systemic chemotherapy.

Adult↗
PubMed1990

c-erbB-2 protein expression in node negative breast cancer.

We investigated the expression of c-erB-2 protein in two matched groups of breast cancer patients, one with and one without relapse. 37 patients with relapse were compared with 42 patients without recurrence for time of observation, adjuvant treatment, age, menopausal status and estrogen receptor content. Paraffin-embedded sections were stained with the polyclonal antibody 21N, raised against a synthetic peptide from the predicted sequence of the c-erbB-2 protein. The staining of c-erbB-2 was measured on a scale of 0 to 3+. C-erbB-2 staining was negative in 16 (38%) patients in the relapse-free group, and in 8 (22%) of the patients with metastases. Neither disease-free survival (DFS) nor overall survival (OS) were dependent upon the extent of c-erbB-2 expression. An analysis by estrogen receptor (ER) status (i.e. positive or negative) and by c-erbB-2 expression (i.e. positive or negative) revealed that patients with ER-positive primaries and negative c-erbB-2 have the longest disease-free survival (DFS) and overall survival (OS). We conclude that c-erbB-2 expression might be clinically useful only if other prognostic variables (e.g. estrogen receptor content in the tumor) are also considered.

Adult↗
PubMed1990

CGS 16949A, a new aromatase inhibitor in the treatment of breast cancer--a phase I study.

Forty-six postmenopausal women with either locally advanced or metastatic breast cancer were treated with the aromatase inhibitor CGS 16949A in three different daily doses (0.3 mg, 0.6 mg and 0.9 mg total daily dose). 41 patients (89%) were pretreated by endocrine treatment for metastatic disease; 30 of these 41 were also pretreated with chemotherapy. Of the remaining 5 patients (11%) 3 were previously treated with chemotherapy alone and 2 were not pretreated. Evaluable sites of disease were: skin and soft tissue (including local recurrence) in 34, bone in 31, lung in 14 and viscera in 13 instances, respectively. 1 PR (3%) and 9 stable diseases (24%) were observed in the 37 patients assessable for response. All but two of these results were observed in the 0.9 mg group. Time to progression was 14 months for the patient showing a PR, and the median time to progression for those with stable disease was 6 months (range 6 to 23 months). Plasma estradiol and estrone levels were measured in patients receiving the daily dose of 0.6 mg (n = 4) and 0.9 mg (n = 15). The estrone levels decreased from a mean of 23.1 pg/mL (SD 17.1) to 10.5 pg/mL (SD 6.6) in the 0.6 mg-group and from 21.2 pg/mL (SD 18.9) to 9.1 pg/mL (SD 5.5) in the 0.9 mg-group within 4 days of drug administration (p less than 0.0001 from baseline in both groups, with no significant difference between doses).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Adjuvant systemic therapy for breast cancer in the elderly: competing causes of mortality. International Breast Cancer Study Group.

Between 1978 and 1981 we conducted a trial in which adjuvant endocrine therapy consisting of tamoxifen (T = 20 mg/d) and low-dose prednisone (p = 7.5 mg/d) for the duration of one year (p + T), was compared with no adjuvant therapy (observation) in 320 women with operable breast cancer aged 66 to 80 years (median age, 70 years). All patients had axillary lymph node metastases after at least a total mastectomy and axillary clearance. At 96 months median follow-up, 9.1% of the patients died without apparent relapse from cancer. An additional 1.9% had a second malignant neoplastic disease (not breast cancer). The 8-year disease-free survival (DFS) percentages (+/- SE) for the p + T and the observation groups were 36% (+/- 4%), and 22% (+/- 3%), (P = .004). The 8-year overall survival percentages were 49% (+/- 4%) and 42% (+/- 4%), respectively (P = .43). We conclude that despite a large proportion of deaths without relapse of breast cancer, a significant advantage for the p + T group in terms of DFS was demonstrated. We hypothesize that an endocrine therapy of longer duration might have an overall survival benefit in a population of elderly patients.

Aged↗
PubMed1989

Comparison of adjuvant therapies using quality-of-life considerations.

The benefit for patients with operable breast cancer treated with adjuvant systemic therapy is small, if reduction of early mortality within the context of randomized control trials is used for treatment comparison. One might consider that the 75%-85% of patients who die despite treatment are overtreated, as are patients who remain alive even without therapy within a given time frame. Larger treatment benefits in terms of avoided or delayed breast cancer relapse have been demonstrated even at early phases of follow-up in the vast majority of adjuvant trials. Exposure of all patients to adjuvant therapy at a time at which no symptoms of disease are present is detrimental in terms of quality of life. Based on our assumption that the quality of life of the patient is typically altered both by subjective toxic effects of adjuvant treatment and by the appearance of relapse, we developed a method of comparing treatment effects in terms of time without symptoms of disease and toxicity of treatment (TWiST). Because the impact of treatment on relapse rates appears earlier than survival effects in all adjuvant therapy trials, and because the value of time without relapse in terms of the quality of life of the patients is as yet poorly defined, we have generalized our method of comparing treatment attitudes to include individual qualitative judgment values. The experience gained from integrating quality-of-life issues into clinical trials for breast cancer might also be applied to other diseases characterized by a chronic course, toxic treatments, and gains in periods of relative or absolute freedom from toxic effects and progressive disease.

Attitude to Health↗
PubMed1989

Costs and benefits of adjuvant therapy in breast cancer: a quality-adjusted survival analysis.

The use of adjuvant chemotherapy for postmenopausal patients with early breast cancer remains controversial because the potential benefits in terms of prolongation of disease-free survival (DFS) and overall survival (OS) must be balanced against the toxicity of treatment. Following mastectomy, 463 evaluable postmenopausal women with node-positive breast cancer were randomized to receive either chemoendocrine therapy for 1 year, or endocrine therapy alone for 1 year, or no adjuvant therapy (Ludwig Trial III). At 7-years median follow-up, OS was longer for the chemoendocrine-treated patients compared with controls (P = .04) and compared with the adjuvant endocrine therapy-alone group (P = .08). In order to balance this therapeutic advantage against the toxic effects of treatment, OS time was divided into time with toxicity (TOX), time without symptoms and toxicity (TWiST), and time after systemic relapse (REL). TOX and REL were weighted by coefficients of utility relative to TWiST and the results added to give a period of quality-adjusted survival (Q-TWiST). Benefits measured by Q-TWiST generally favored chemoendocrine therapy. For example, if TOX and REL were both given utility coefficients of 0.5 relative to 1.0 for TWiST, then by 7 years the average Q-TWiST for chemoendocrine therapy was 6.7 months longer than for no-adjuvant therapy (P = .05) and 4.1 months longer than for endocrine therapy alone (P = .20). Quality-adjusted survival analysis is recommended in assessing costs and benefits of toxic adjuvant therapy. In this example, it supports the use of chemoendocrine therapy in postmenopausal node-positive patients for a wide range of relative values assigned to periods with symptoms and toxicity.

Antineoplastic Agents↗
PubMed1989

A quality-of-life-oriented endpoint for comparing therapies.

An endpoint, time without symptoms of disease and toxicity of treatment (TWiST), is defined to provide a single measure of length and quality of survival. Time with subjective side effects of treatment and time with unpleasant symptoms of disease are subtracted from overall survival time to calculate TWiST for each patient. The purpose of this paper is to describe the construction of this endpoint, and to elaborate on its interpretation for patient care decision-making. Estimating the distribution of TWiST using actuarial methods is shown by simulation studies to be biased as a result of induced dependency between TWiST and its censoring distribution. Considering the distribution of TWiST accumulated within a specified time from start of therapy, L, allows one to reduce this bias by substituting estimated TWiST for censored values and provides a method to evaluate the "payback" period for early toxic effects. Quantile distance plots provide graphical representations for treatment comparisons. The analysis of Ludwig Trial III evaluating toxic adjuvant therapies versus a no-treatment control group for postmenopausal women with node-positive breast cancer illustrates the methodology.

Antineoplastic Agents↗
PubMed1988

Treatment of advanced ovarian cancer with surgery, chemotherapy, and consolidation of response by whole-abdominal radiotherapy.

Between April 1981 and June 1985, 195 patients with ovarian cancer, International Federation of Gynecology and Obstetrics (FIGO) Stages IIB, IIC, III, and IV, entered a trial that consisted of surgery and chemotherapy with cisplatin (P) and melphalan (PAM) with or without hexamethylmelamine (HexaPAMP or PAMP regimens) every 4 weeks for 6 cycles. Because the intent was to study the outcome by treatment after evaluation of first-line chemotherapy, patients were evaluable only if the response was assessed by a second-look operation or if measurable disease progression was documented. One hundred fifty-eight patients (81%) were evaluable for response. Forty-five (28%) achieved pathologically confirmed complete remissions (pCR), and 24 of these patients received whole-abdominal radiation (WAR) for consolidation of response. Five patients with complete remission after WAR relapsed, as did nine of the 21 with complete remission who had not undergone WAR. The 3-year time to progression percentage (TTP +/- SE) from second-look operation was 70% +/- 7% for all patients who achieved pCR, 83% +/- 8% for those who received WAR, and 49% +/- 15% for those who did not receive WAR (this was not a randomized comparison). The 3-year TTP percentage for the 49 partial responders was 21% +/- 6%, identical for the 19 who had WAR and the 30 who had no radiation therapy. Additional or alternative methods for consolidation of pCR are needed since patients continue to relapse despite optimal initial response to therapy.

Abdomen↗
PubMed1988

Ovarian cancer and tumor markers: sialic acid, galactosyltransferase and CA-125.

In an effort to correlate the serum values of potential markers, including CA-125, galactosyltransferase, and total sialic acid, with residual tumor mass after initial surgery, 43 patients with FIGO stage IIb and c, III and IV ovarian cancer were studied. The sensitivity of galactosyltransferase and sialic acid levels was sufficient to correlate their serum values with the corresponding residual tumor mass. Furthermore, 28 patients were histopathologically evaluated for their response to chemotherapy. Determination of these tumor markers did not permit discrimination between small residual disease (less than or equal to 1 cm) and a state of 'no evidence of disease'. Conversely, progression of disease has been associated with a sensitive increase in the level of all three markers. CA-125 has been found to be the most useful of the three for distinguishing between responders and nonresponders.

Antigens, Neoplasm↗
PubMed1988

Relapse of breast cancer after adjuvant treatment in premenopausal and perimenopausal women: patterns and prognoses.

Eight hundred eighteen premenopausal or perimenopausal breast cancer patients with axillary node metastases were treated with adjuvant chemotherapy (CMF) with or without endocrine treatment (prednisone, oophorectomy) in two concurrent prospective trials. Three hundred fifty-two (43%) had recurrent disease at a median follow-up time of 6 years. The 2-year survival percentages from time of first relapse were 16% for patients with initial metastases in visceral or multiple sites (including bone and soft tissue), 41% for those with regional metastases or skeletal relapse alone and 70% for patients with isolated local recurrence or contralateral breast cancer. The features that most influenced prognosis within the categories defined by site of first relapse were disease-free interval (less than 24 months v greater than or equal to 24 months), and estrogen receptor content in the primary tumor. These features had clinical importance (identifying patients with at least a 50% 2-year survival percentage) only in those patients with local, contralateral breast, regional, or bony disease alone. The treatment of individual patients after relapse must be directed toward optimized palliation. The results of this study are important for defining groups of patients who relapse after CMF for whom the subsequent therapeutic approach might be differentiated (eg, experimental treatments for dire prognosis, accent on minimal side effect treatment for intermediate prognosis, and investigation of adjuvant systemic therapy for isolated local recurrence).

Antineoplastic Combined Chemotherapy Protocols↗