Showing papers by "Michael J. Baum published in 2005"
TL;DR: The 10-year and 15-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival are reported and it is found that the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis.
6,309 citations
TL;DR: Time to recurrence was longer for anastrozole- than tamoxifen-treated patients in both ER+/PgR+ and ER-/Pg R- subgroups, but the benefit was substantially greater in the PgR- subgroup.
Abstract: Purpose Arimidex, tamoxifen alone, or in combination (ATAC) trial of anastrozole (Arimidex) versus tamoxifen or a combination of the two in 9,366 postmenopausal patients with primary breast cancer found a significant improvement in disease-free survival and time to recurrence (TTR) for anastrozole compared with tamoxifen, that was restricted to patients with hormone receptor-positive (ie, estrogen receptor–positive [ER+] and/or progesterone receptor-positive [PgR+]) disease, the target population for these therapies. We retrospectively tested the hypothesis that this benefit might differ according to PgR status. Patients and Methods TTR was compared between the three treatment groups for subgroups defined by ER and PgR status using Cox's proportional hazards model, with and without adjustment for baseline variables. Results The unadjusted hazard ratio (HR) for anastrozole versus tamoxifen for TTR was 0.74 (95% CI, 0.64 to 0.87) for women with either ER+ or PgR+ tumors. In the ER+/PgR+ subgroup (n = 3,834)...
251 citations
TL;DR: Informed consent for randomization was difficult to obtain, leading to the exclusion of eligible patients, and it is therefore proposed to include non‐randomized patients in a total cohort study.
Abstract: Three hundred and eighty-one women with operable breast cancer aged over 70 years were randomly allocated to 40 mg tamoxifen daily and optimal surgery or to tamoxifen alone. At a median follow-up of 34 months there was no demonstrable difference in survival rate or in quality of life between the two treatment groups. More patients treated with tamoxifen alone had a subsequent change of management and this was usually an operation for local treatment failure. This progression to surgery has not been shown to be disadvantageous and the study will continue. Informed consent for randomization was difficult to obtain, leading to the exclusion of eligible patients, and it is therefore proposed to include non-randomized patients in a total cohort study.
182 citations
TL;DR: It is suggested that ferrets may use urine marking for sex and individual recognitions, and most of the major compounds in anal glands were not present in urine, which suggests that urine may convey specific signals that differ from those of anal glands.
Abstract: Quantitative stir bar sorptive extraction methods, both in the aqueous and headspace modes, followed by thermal desorption gas chromatography-mass spectrometry were used to investigate individual variations in the volatile components of male and female ferret (Mustela furo) urine. The urinary profiles were further compared with volatile profiles of anal gland secretions of breeding male and female ferrets. Thirty volatile compounds were quantified in male and female urine. Among them, 2-methylquinoline was unique to male urine. Four ketones (4-heptanone, 2-heptanone, o-aminoacetophenone, and a dimethoxyacetophenone) and several nitrogen compounds (e.g., 2,5-dimethylpyrazine, quinoline, 4-methylquinazoline) and low levels of three unidentified nonsulfur compounds were significantly more abundant in males than in females. Quantitative comparison of 30 volatile urinary compounds showed several statistically significant differences between the sexes and individuals of the same sex. These findings suggest that ferrets may use urine marking for sex and individual recognitions. Ten of the 26 compounds identified in anal gland secretions from females and males were also found in urine. However, most of the major compounds (thietanes, dithiolanes, and indole) in anal glands were not present in urine. This suggests that urine may convey specific signals that differ from those of anal glands. Additionally, 10 volatiles (two aldehydes, five ketones, benzothiazole, 2-methylquinoline, and 4-methylquinazoline), not previously identified, were found in ferret anal gland secretions. Among the new compounds, o-aminoacetophenone was found only in males, while only traces of this compound were found in females. Similar results were previously obtained in anal glands of three other Mustela species. These findings provide new information about the constituents of urine and volatile components of anal gland secretions in ferrets.
100 citations
76 citations
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41 citations
TL;DR: Patients treated with adjuvant tamoxifen therapy will show a delay in the appearance of recurrent disease with a reduced response to further tamoxIFen therapy, and the model may provide an in vivo method to examine the relationships between oestrogen and progesterone receptors and response to endocrine therapy.
Abstract: There is very little known about the subsequent behavior of breast cancer following adjuvant endocrine therapy or the effect of this therapy on the oestrogen and progesterone receptor content of recurrent disease. Mammary tumours were induced in Sprague-Dawley rats using N-nitrosomethylurea. In two experiments animals were treated with tamoxifen at different doses prior to the appearance of tumours. Tamoxifen prolonged the induction time and reduced the total number of tumours. Subsequent treatment of established tumours exposed to tamoxifen in the induction period demonstrated a reduced response to further tamoxifen therapy. There was no difference in the oestrogen receptor content of the tumours previously exposed to tamoxifen, but there was a significant reduction in the progesterone receptor content. The results suggest that: (a) patients treated with adjuvant tamoxifen therapy will show a delay in the appearance of recurrent disease with a reduced response to further tamoxifen therapy; (b) the model may provide an in vivo method to examine the relationships between oestrogen and progesterone receptors and response to endocrine therapy.
24 citations
19 citations
TL;DR: A multicentre, prospective trial on the treatment of Stage‐I and Stage‐II breast cancer bysimple mastectomy plus radiotherapy versus simple mastectomy alone is described, finding thatillary lymph‐nodes have regressed within 3 months of mastectomy in 75 per cent of patients in clinical Stage II.
Abstract: A multicentre, prospective trial on the treatment of Stage-I and Stage-II breast cancer by simple mastectomy plus radiotherapy versus simple mastectomy alone is described. So far 1050 patients have been collected within 2 years. Data on the first 161 patients treated by simple mastectomy alone are analysed. Axillary lymph-nodes have regressed within 3 months of mastectomy in 75 per cent of patients in clinical Stage II. Regression may be due to resolution of reactive changes in lymph-nodes following removal of the primary tumour.
16 citations
TL;DR: A possible explanation for the reduction in the first peak with anastrozole relates to the fact that COX2 expression, a natural response to wounding, leads indirectly to the activation of the aromatase enzyme, therefore, an AI might in part suppress theactivation of dormant metastases by the act of surgery.
Abstract: Background: The hazard rate (HR) for relapse following primary surgery for breast cancer demonstrates two peaks. The first, and steepest, peak occurs at approximately 18-24 months after surgery and may result from the activation of dormant/latent metastases by the initiation of angiogenesis, the expression of the genetic mechanisms responsible for wound healing, and the induction of proliferative activity in single quiescent tumor cells through growth factors. The second, flatter, peak occurs approximately 5-6 years after surgery and is thought to result from the stochastic transition of occult metastases from a latent to an active state, representing an "echo" of the natural history of the original disease. Method: The ATAC trial compared 5 years of adjuvant tamoxifen (T) versus 5 years of adjuvant anastrozole (A), a third-generation aromatase inhibitor (AI), in women with early breast cancer, and 68-month follow-up data were reported in December 2004. Here, we compare this data with a matched series from the Milan Institute database of patients, who were treated before the introduction of systemic adjuvant therapy to produce a semi-quantitative comparison. Results: The shape and timing of the signal for HR were identical for each of the three data sets (T, A and Milan), with the first peak at 18-24 months and the second peak beginning to appear at 4-5 years following primary therapy. However, in the T and A groups, the peaks were substantially flattened. The most striking aspect of our comparison was the near-obliteration of the first peak in the A group. Conclusion: A possible explanation for the reduction in the first peak with anastrozole relates to the fact that COX2 expression, a natural response to wounding, leads indirectly to the activation of the aromatase enzyme. Therefore, an AI might in part suppress the activation of dormant metastases by the act of surgery. If this is the case, AIs should be initiated at (or even before) surgery in order to optimize this effect. Furthermore, this benefit might be enhanced by the concomitant use of a COX2 inhibitor.
TL;DR: This study suggests that surgery has both a qualitative (IVMLP) and quantitative (monocyte counts) effect on the mononuclear phagocytes, which may be relevant when considering factors that influence the early stages of wound healing.
Abstract: In vitro monocyte lysozyme production (IVMLP) was assessed in 10 male patients preoperatively and at intervals postoperatively. A similar procedure was carried out in 6 sex- and age-matched controls. In contrast to the control group where the IVMLP was constant, the IVLMP levels in the surgical group showed a marked increase at 6-10 h postoperatively, falling to control levels after 10 days. In addition, peripheral monocyte counts were carried out using a Technicon Hemalog D counter which produces accurate reproducible counts for cells such as monocytes which occur at low frequency. The peripheral monocyte counts were stable in the control group, whilst in the surgical patients there were significantly higher readings at 36-48 h, which persisted for up to 10 days compared with preoperative counts. This study suggests that surgery has both a qualitative (IVMLP) and quantitative (monocyte counts) effect on the mononuclear phagocytes. These data may be relevant when considering factors that influence the early stages of wound healing.
TL;DR: The present observation that glomerular density, number and area were greater in the caudal MOB of male than female ferrets is inversely correlated with the previous observation that greater odor-induced glomersular activation in the ventral-caudal M OB of female than male ferrets was observed.