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Biomedical subjects

G M Clark

Publications and source records attributed to G M Clark.

At least 163 records · Page 9Linked to original sources
PubMed1996

Prognostic value of Ki-67 compared to S-phase fraction in axillary node-negative breast cancer.

The primary purpose of this study was to evaluate the prognostic significance of Ki-67, a cell proliferation-associated antigen, in a large group (n = 674) of axillary node-negative breast cancer cases with long-term follow-up and to correlate Ki-67 antigen expression with S-phase fraction. Ki-67 immunostaining was assessed both semiquantitatively and quantitatively. The statistical analysis focused on agreement between methods of Ki-67 quantification, agreement between Ki-67 and S-phase fraction, associations between Ki-67 and other clinical variables, and prognostic value of Ki-67. There was excellent agreement between the two methods of Ki-67 assessment (Spearman rank correlation, rsp = 0.91; P = 0.0001; n = 674) but only weak correlation between either semiquantitative or quantitative Ki-67 and S-phase fraction (rsp = 0.12 and rsp = 0.15, respectively). Ki-67 (overall median, 2%) was independent of tumor size and modestly related to other measures of tumor aggressiveness. Using a cutpoint of 5% (percentage of tumor cells), cases with high Ki-67 exhibited a significantly shorter disease-free survival (Padj = 0.004). In multivariate analysis, high Ki-67 was associated with a 1.8-fold increased risk of recurrence (P = 0.001). In the subgroup with S-phase data, the adjusted relative risk (hazard ratio, 1.9; P = 0.02) was unchanged by inclusion of S phase in the model. This suggests that Ki-67 provides significant independent prognostic information in addition to that contained in tumor size and S-phase fraction.

Breast Neoplasms↗
PubMed1996

The small heat shock protein HSP27 is not an independent prognostic marker in axillary lymph node-negative breast cancer patients.

Heat shock protein 27 (hsp27) belongs to the family of heat shock proteins and is thought to be involved in thermotolerance, cell proliferation, drug resistance, and chaperone processes. The aim of this study was to investigate whether hsp27 levels are correlated with clinical outcome in axillary lymph node-negative breast cancer patients. We describe a Western blot study measuring hsp27 levels in 425 patients and an immunohistochemistry (IHC) study analyzing 788 patients. Results obtained by both methods were concordant. Univariate survival analysis was performed considering hsp27 either as an optimally dichotomized variable or as a continuous variable. Additional data include age at biopsy, tumor size, estrogen receptor (ER) and progesterone receptor status, tumor ploidy and percentage of cells in S phase, and adjuvant therapy. hsp27 levels correlated positively with ER status (P = 0.0001 in Western blot and IHC study), progesterone receptor status (P = 0.0001 in Western blot and IHC study), and aneuploidy (Western blot study, P = 0.0012; IHC study, P = 0.0004) but not with tumor size (Western blot study, P = 0.69; IHC, P = 0.53) or S phase (Western blot study, P = 0.19; IHC study, P = 0.38). Overall, there was no relationship between hsp27 expression and disease-free survival (Western blot study, P = 0.70/0.54; IHC, P = 0.47/0.30) or overall survival (Western blot study, P = 0.16/0.15; IHC, P = 0.46/0.78). Exploratory subset analyses defined by ER status and use of adjuvant treatment indicated that in ER+/untreated patients, high hsp27 levels correlated modestly with shorter disease-free survival (Western blot, P = 0.04/0.04; IHC, P = 0.11/0. 03). hsp27 is not a useful prognostic marker for the clinic in axillary lymph node-negative patients. However, the finding of modest prognostic value of hsp27 in the subgroup of ER+/untreated patients raises new questions about the biological function of hsp27 in breast cancer.

Adult↗
PubMed1995

Randomised trial of lipid lowering dietary advice in general practice: the effects on serum lipids, lipoproteins, and antioxidants.

OBJECTIVE: To determine the relative efficacy in general practice of dietary advice given by a dietitian, a practice nurse, or a diet leaflet alone in reducing total and low density lipoprotein cholesterol concentration. DESIGN: Randomised six month parallel trial. SETTING: A general practice in Oxfordshire. SUBJECTS: 2004 subjects aged 35-64 years were screened for hypercholesterolaemia; 163 men and 146 women with a repeat total cholesterol concentration of 6.0-8.5 mmol/l entered the trial. INTERVENTIONS: Individual advice provided by a dietitian using a diet history, a practice nurse using a structured food frequency questionnaire, or a detailed diet leaflet sent by post. All three groups were advised to limit the energy provided by fat to 30% or less and to increase carbohydrate and dietary fibre. MAIN OUTCOME MEASURES: Concentrations of total cholesterol and low density and high density lipoprotein cholesterol after six months; antioxidant concentration and body mass index. RESULTS: No significant differences were found at the end of the trial between groups in mean concentrations of lipids, lipoproteins, and antioxidants or body mass index. After data were pooled from the three groups, the mean total cholesterol concentration fell by 1.9% (0.13 mmol/l, 95% confidence interval 0.06 to 0.22, P < 0.001) to 7.00 mmol/l, and low density lipoprotein cholesterol also fell. The total carotenoid concentration increased by 53 nmol/l (95% confidence interval 3.0 to 103, P = 0.039). CONCLUSIONS: Dietary advice is equally effective when given by a dietitian, a practice nurse, or a diet leaflet alone but results in only a small reduction in total and low density lipoprotein cholesterol. To obtain a better response more intensive intervention than is normally available in primary care is probably necessary.

Antioxidants↗
PubMed1995

Urokinase receptor in breast cancer tissue extracts. Enzyme-linked immunosorbent assay with a combination of mono- and polyclonal antibodies.

Urokinase plasminogen activator (uPA) is a proteolytic enzyme involved in degradation of the extracellular matrix during cancer invasion. The levels of uPA and its inhibitor PAI-1 in tumor extracts have previously been demonstrated to be of prognostic value in breast cancer as well as other types of cancer. We have previously characterized a specific cell surface receptor for uPA (uPAR) which strongly enhances the catalytic activity of uPA and is expressed during mammary cancer invasion. In order to quantitate uPAR in breast cancer tissue, we have now developed a sensitive enzyme-linked immunosorbent assay (ELISA), with polyclonal catching antibodies and three monoclonal detecting antibodies. The detection limit of the assay is approximately 0.16 fmol of uPAR in a volume of 100 microliters (1.6 pM). There is a linear relationship between signal and uPAR concentration up to at least 6.6 fmol per 100 microliters (66 pM). Both free uPAR and uPAR in complex with uPA is detected. The recovery of an internal uPAR standard in breast cancer tissue extracts is above 87%. The intra-assay and inter-assay variation coefficients are 7% and 13%. In order to find a suitable buffer for extraction of various components of the uPA-system from breast cancer tissue, we tested buffers which previously have been used for optimal extraction of estrogen receptor (A), uPA (B), and uPAR (C). Buffer A and B extracted approximately 30% and 50%, respectively, of the amount of uPAR extracted with buffer C.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Activity of the morpholino anthracycline 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming units in vitro.

In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 micrograms/ml either for 1 hour (2-1 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19% in vitro response at 0.05 micrograms/ml and 69% at 0.5 micrograms/ml) than with 1-hour exposure (1.3% at 0.05 micrograms/ml and 12% at 0.5 micrograms/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 micrograms/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity with those tumors.

Antibiotics, Antineoplastic↗
PubMed1995

Adenocarcinoma of unknown primary: retrospective analysis of chemosensitivity of 313 freshly explanted tumors in a tumor cloning system.

Cancer of unknown primary origin is the eighth most common form of malignancy and accounts for up to 10% of all neoplasms diagnosed. It is a set of heterogenous tumors with widely varying sensitivity to systemic chemotherapy. Over the past years progress has been made in identifying subsets of patients that can be effectively treated with chemotherapy and may achieve long-term survival even with metastatic disease. However, the large majority of cancers of unknown origin still is resistant to chemotherapy. In an attempt to identify conventional and investigational new agents with possible activity against cancers of unknown primary, we have retrospectively analyzed the results of chemosensitivity testing in a soft agar cloning system in vitro and have compared these data with published clinical trials. Between 1978 and 1993, a total of 19584 tumor specimens were studied using a variety of investigational or established antitumor agents. Of these, 615 (3.1%) were tumors of unknown origin and confirmed on pathology review. The largest histologic subgroup was adenocarcinoma (332, 54%). Sufficient numbers of cells for in vitro testing were obtained from 313 tumor specimens (94.3%). Of 278 agents tested in adenocarcinoma of unknown origin, borderline activity (< 20% in vitro response) was noted for 5-FU, doxorubicin, bleomycin, mitoxantrone, mitomycin-C, cisplatin, and etoposide. In vitro response rates of > or = 20% were observed for actinomycin-D, BCNU, melphalan, methotrexate, taxol, and vinblastine. In addition, several investigational agents including fludarabine, amira235, bisantrene, Dupont840, echinomycin, tiazofurin, LY104208 (vinzolidine), intoplicine, and topotecan had activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates.

While recent studies have suggested that electrical stimulation of the auditory nerve at high stimulus rates (e.g., 1000 pulses/s) may lead to an improved detection of the fine temporal components in speech among cochlear implant patients, neurophysiological studies have indicated that such stimulation could place metabolic stress on the auditory nerve, which may lead to neural degeneration. To examine this issue we recorded the electrically evoked auditory brainstem response (EABR) of guinea pigs following acute bipolar intracochlear electrical stimulation using charge-balanced biphasic current pulses at stimulus rates varying from 100 to 1000 pulses/s and stimulus intensities ranging from 0.16 to 1.0 microC/phase. Charge density was held constant (approximately 75 microC cm-2 geom/phase) in those experiments. To monitor the recovery in excitability of the auditory nerve following this acute stimulation. EABR thresholds, wave I and III amplitudes and their latencies were determined for periods of up to 12 h following the acute stimulation. Higher stimulus rates and, to a lesser extent, higher intensities led to greater decrements in the post-stimulus EABR amplitude and prolonged the recovery period. While continuous stimulation at 100 pulses/s induced no decrement in the EABR, stimulation at 200 and 400 pulses/s produced an increasingly significant post-stimulus reduction of the EABR amplitude, which showed only partial recovery during the monitoring period. No EABR response could be evoked immediately following stimulation at 1000 pulses/s, using a probe intensity 16-19 dB below the stimulus intensity. However, partial EABR recovery was observed for wave III following stimulation at the lowest stimulus intensity (0.16 microC/phase). These stimulus-induced reductions in the EABR amplitude were also reflected in increased thresholds and latencies. Providing stimulus rate and intensity were held constant, stimulation at different charge densities (37.7, 75.5 and 150.7 microC cm-2 geom/phase) had no influence on the post-stimulus EABR recovery. Significantly, the introduction of a 50% duty cycle into the stimulus pulse train resulted in a more rapid and complete post-stimulus recovery of the EABR compared to continuous stimulation. These data suggest that stimulus rate is a major contributor to the observed reduction in excitability of the electrically stimulated auditory nerve. This reduction may be a result of an activity-induced depletion of neural energy resources required to maintain homeostasis. The present findings have implications for the design of safe speech-processing strategies for use in multichannel cochlear implants.

Animals↗
PubMed1995

Immunofluorometric analysis of p53 protein and prostate-specific antigen in breast tumours and their association with other prognostic indicators.

Mutation and overexpression of p53 occurs in 20-40% of breast cancers and has been shown to be an independent prognostic indicator. Recently we have demonstrated prostate-specific antigen (PSA) expression in breast tumours to be suggestive of favourable prognosis, but quantitative relationships between PSA and p53, and between these and other prognostic factors in breast cancer, have not been investigated. Time-resolved immunofluorometric procedures were used to quantify both p53 protein and PSA in 200 breast tumour extracts, which were also assayed for oestrogen (ER) and progesterone receptors (PGR), epidermal growth factor receptors (EGFR), cathepsin D and HER-2/neu, and characterised for S-phase fraction and DNA ploidy. Weak Spearman correlations were found between p53 and ER (r = - 0.18, P = 0.010), PGR (r = - 0.15, P = 0.0385) and S-phase fraction (r = 0.17, P = 0.016), while PSA was correlated only with PGR (r = 0.16, P = 0.025). Wilcoxon rank sum analysis revealed that levels of ER (P = 0.0001), PGR (P = 0.0001), S-phase fraction (P = 0.0001) and EGFR (P = 0.0014) differed significantly between the two groups categorised as p53 negative or p53 positive. Tumours classified as PSA negative or PSA positive were found to differ with respect to PGR (P = 0.0091) and S-phase fraction (P = 0.011) in a similar analysis. Contingency tables indicated significant negative associations between the status of p53 and that of ER (P = 0.003) and PGR (P = 0.001) and between PSA and S-phase fraction (P = 0.012), and positive associations between p53 and EGFR (P = 0.017), HER-2/neu (P = 0.008), S-phase fraction (P = 0.001) and aneuploidy (P = 0.007), and between PSA and both ER (P = 0.061) and PGR (P = 0.010). No significant associations were found between p53 and PSA. Our results demonstrate that the presence of p53 in breast tumours relates to several other variables which are suspected to predict aggressive tumour phenotypes and that the presence of PSA relates to variables associated with good prognosis.

Breast Neoplasms↗
PubMed1995

Articulation accuracy of children using an electrotactile speech processor.

OBJECTIVE: Use of wearable tactile speech perception devices is suggested to help overcome the difficulties in speech production resulting from severe and profound hearing impairment in children. This suggestion is based on the assumption that subjects can use tactile input in isolation, or in combination with information from residual aided hearing, to monitor and modify their speech. The present study evaluated the benefits to articulation provided through use of a multichannel electrotactile device ("Tickle Talker"). DESIGN: Six profoundly hearing-impaired children were videotaped speaking with the Tickle Talker on and with the Tickle Talker off during conversations with their audiologist. Five of the subjects also wore their binaural hearing aids during all recorded conversations. The number of vowels, consonants, and overall phonemes correctly articulated by each child in the two conditions were compared. RESULTS: One subject improved articulation of initial consonants and initial phonemes; one subject improved articulation of total vowels, total consonants, initial consonants, total phonemes, and initial phonemes; and a third subject improved articulation of total vowels and medial phonemes. CONCLUSIONS: Use of on-line tactile feedback from the Tickle Talker may benefit the articulation accuracy of some children, and the device may therefore be suitable to use with children who have not responded to more traditional speech training techniques.

Adolescent↗
PubMed1995

A clinical report on receptive vocabulary skills in cochlear implant users.

OBJECTIVES: The aim was to measure the rate of vocabulary acquisition for cochlear implant users and compare the pre- and postoperative rates with published data for other groups with normal or impaired hearing. The hypothesis was that the postoperative rate would be greater than the preoperative rate. DESIGN: The Peabody Picture Vocabulary Test (PPVT) was administered to 32 children, adolescents, and prelinguistically deafened adults implanted with the 22-electrode cochlear implant. Age at implantation ranged from 2 yr 6 mo to 20 yr and implant use ranged from 6 mo to 7 yr 8 mo. RESULTS: The group mean postoperative performance at various postoperative intervals was significantly higher than mean preoperative performance. Single-subject data indicated statistically significant gains over time on this test for 13 of the subjects. The mean postoperative rate of vocabulary acquisition of 1.06 times the rate for normally hearing children was significantly greater than the mean preoperative rate of 0.43. CONCLUSION: These rates of improvement were in accord with previous reports on smaller numbers of implant users, but could not be attributed unambiguously to use of the implant because no control group was used for this clinical work. Variables such as age at implantation, duration of profound deafness, communication mode, and speech perception skill failed to significantly predict rate of improvement of the PPVT.

Adolescent↗
PubMed1995

The automated prediction of hearing thresholds in sleeping subjects using auditory steady-state evoked potentials.

OBJECTIVE: To examine the relationship between auditory steady-state evoked potentials (SSEPs) and behavioral thresholds in sleeping subjects. DESIGN: 60 adults and children with hearing thresholds ranging from normal to profound were selected on the basis of appropriate audiograms. Behavioral audiograms were determined at the octave frequencies 250-4000 Hz. These behavioral thresholds were then compared with the SSEP thresholds obtained during natural sleep for adults, or natural or sedated sleep for children. RESULTS: A strong relationship between behavioral and SSEP thresholds was observed. The strength of the relationship increased with increasing frequency and increasing degree of the loss. On the basis of these data, the prediction of behavioral thresholds from SSEP levels was determined. It was found that the standard deviation of the error in this prediction decreased with increasing frequency and increasing degree of the loss. There was no significant age effect in the results obtained at any of the frequencies. CONCLUSION: The results suggest the SSEP technique can be used as a predictor of behavioral threshold in adults and children at the frequencies 250-4000 Hz.

Adult↗
PubMed1995

A clinical report on speech production of cochlear implant users.

OBJECTIVE: The aim was to assess articulation and speech intelligibility over time in a group of cochlear implant users implanted at 8 yr or over. The hypothesis was that the postoperative speech production performance would be greater than the preoperative performance. DESIGN: A test of intelligibility using sentences and an articulation test measuring non-imitative elicited speech were administered to 11 and 10 subjects, respectively, who were implanted with the 22-electrode cochlear implant. Nine subjects received both tests. Age at implantation ranged from 8 yr to 20 yr and implant use ranged from 1 yr to 4 yr 5 mo. RESULTS: For both the intelligibility and articulation tests roughly half of the subjects showed significant improvements over time and group mean postoperative performance significantly exceeded preoperative performance. Improvements occurred for front, middle, and back consonants; for stops, fricatives, and glides and for voiceless and voiced consonants. CONCLUSIONS: Despite being deprived of acoustic speech information for many childhood years, roughly half of the patients assessed showed significant gains in speech intelligibility and articulation postimplantation. The lack of a control group of non-implanted patients means that we cannot separate out the influence of the implant on speech production from other influences such as training and tactile-kinaesthetic feedback.

Adolescent↗
PubMed1995

Comparison of age-related changes in short-wavelength-sensitive cone thresholds between normals and patients with primary open-angle glaucoma.

PURPOSE: To establish the effect of aging upon short-wavelength-sensitive cone (S-cone) sensitivity for both normals and patients with primary open-angle glaucoma (POAG). METHODS: S-cone thresholds were established for the detection of blue test spots on a bright yellow adapting background. Detection thresholds for combined medium- and long-wavelength-sensitive cones (M/L-cones) were also established for a yellow test spot upon a yellow background. A group of 177 normal subjects (age range 20 to 80 years) and 46 glaucoma subjects were examined. RESULTS: The rate of decline of S-cone sensitivity with increasing age was found to be similar in patients with POAG and age-matched normals (approximately 0.2 log units/decade), although S-cone sensitivity in the POAG population was significantly lower (p < 0.05) than that in age-matched normals by approximately 0.3 log units. CONCLUSIONS: The results of the present investigation show an age-related decline in S-cone sensitivity for both normals and patients with POAG. The decline in S-cone sensitivity within the POAG population is similar to that occurring in normal subjects when the two populations are matched for age.

Adult↗
PubMed1995

Evaluation of a portable two-microphone adaptive beamforming speech processor with cochlear implant patients.

A two-microphone noise reduction technique was tested with four cochlear implant patients. The noise reduction technique, known as adaptive beamforming (ABF), used signals from only two microphones--one behind each ear--to attenuate sounds not arriving from the direction directly in front of the patient. The algorithm was implemented in a portable digital signal processor, and was compared with a strategy in which the two microphone signals were simply added together (two-microphone broadside strategy). Tests with the four patients were conducted in a soundproof booth with target speech arriving from in front of the patient and multitalker babble noise arriving at 90 deg to the left. Results at 0-dB signal-to-noise level (S/N) showed large improvements in speech intelligibility for all patients, when compared to the two-microphone broadside strategy. Precautions were taken to avoid cancellation of the target speech, and, accordingly, subjective tests showed no deterioration in performance for the adaptive beamformer in quiet. Physical measurement of the directional characteristics of the ABF was made with the microphones placed behind the ears of a KEMAR manikin and in the same acoustic environment as used with the patients. Results showed directional gain of approximately 10 dB when the angle of incidence for interfering noise was shifted more than 20 to 30 deg from directly in front of or behind the manikin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amplifiers, Electronic↗
PubMed1995

Pitch matching of amplitude-modulated current pulse trains by cochlear implantees: the effect of modulation depth.

An experiment was conducted with four cochlear implantees, which investigated the pitch evoked by amplitude-modulating current pulse trains delivered to a single cochlear location. These stimuli produce a pitch percept which may be similar to that of acoustic stimuli such as modulated noise for modulation frequencies in the range 80-300 Hz, approximately. The experiments investigated the effect of modulation depth on the way pitch was matched to that of unmodulated pulse trains. The method of constant stimuli was used, in which the variable parameter was the rate of the unmodulated stimulus. The modulated stimuli comprised pulses having one of two possible current values, with the higher value occurring once in every modulation period. The results showed that the matched rate fell exponentially from a value close to the carrier rate towards a value equal to the modulation frequency as the modulation depth increased. The results were compared to the predictions of a simple model in which the matched rate corresponded to a weighted average of carrier and modulation frequencies, with the weightings proportional to the number of neurons firing at each of these frequencies. The results agreed with the predictions of the model reasonably well, except in cases where the carrier rate was 700 Hz or higher, and for one subject at the highest intensity level.

Adult↗
PubMed1995

Responses of dorsal cochlear nucleus single units to electrical pulse train stimulation of the auditory nerve with a cochlear implant electrode.

In response to 100-ms duration electrical stimulation within the range 50-400 pulses per second (pps), and at 1.6- to 2.4-mA stimulus current, a range of poststimulus time histogram (PSTH) patterns were observed from dorsal cochlear nucleus (DCN) units, they were usually primarylike, onset or "negative response" and occasionally buildup or pauser patterns. It appeared that the excitatory and suppressive processes, also termed neural drives, in response to 2.5-pps electrical stimulation were the main determinants of DCN unit responses to 50- to 400-pps stimulation. This was demonstrated by a model of DCN responses to electrical stimulation of the auditory nerve. The neural drives required to model the PSTH patterns were (i) an excitatory process with a latency of < 5 ms, (ii) a second excitatory process latency of 4.5-10 ms, (iii) a long acting suppressive process with a latency of < 15 ms and a duration of > 70 ms, (iv) a short acting suppressive response with a latency of 2.5-3.7 ms and a duration usually < 5 ms, but always < 20, and (v) a drive contributing spontaneous activity to the unit. In addition to these processes which were observed at 2.5 pps, an additional, transient suppressive process was postulated to operate only at 50-400 pps. It was postulated that the PSTH patterns observed were due to differences in the strengths of these drives between units.

Animals↗
PubMed1995

Rapid in vitro assay for predicting response to fluorouracil in patients with metastatic breast cancer.

PURPOSE: To determine if a rapid 3H-uridine uptake assay using breast tumor cells from biopsy specimens could predict clinical response to fluorouracil (5FU) in patients with metastatic breast cancer. PATIENTS AND METHODS: A double-blind prospective study was conducted of 60 patients with measurable, metastatic breast cancer who had failed to respond to at least one prior chemotherapy regimen. Patients received 5FU 300 mg/m2/d by continuous infusion and were monitored for response. Tumor cells from biopsy specimens were grown in microwells and exposed for 3 days to 0.1, 1.0, 10.0, and 100.00 micrograms/mL of 5FU on strips coated with drug and extracellular matrix. Cells were pulsed with 3H-uridine overnight. Incorporated radioactivity was compared for wells with and without drug. Results were available 4 days from specimen submission. RESULTS: Of 45 eligible patients, 11 (24%) were not assessable in vitro. Nine patients were assessable in vitro, but not clinically. Of the remaining 25 patients, who were assessable both clinically and in vitro, there was one complete response (CR), five partial responses (PRs), five cases of stable disease, and 14 cases of progressive disease, for an objective response rate of 24%. Response in vitro was significantly correlated with clinical response (P = .002). Of six clinical responders, five also responded in vitro, for an assay sensitivity of 83%. Of 19 nonresponders, 17 were nonresponders in vitro, for a specificity of 89%. The positive predictive value of the test was 71% (five of seven), and the negative predictive value was 94% (17 of 18). CONCLUSION: Results of an in vitro assay were significantly correlated with clinical response in patients with metastatic breast cancer treated with continuous infusion 5FU.

Breast Neoplasms↗