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Abramson Cancer CenterNCI CANCERLIT® Search: Chemotherapy for Breast Cancer - February 2002
National Cancer Institute®
Last Modified: February 1, 2002
Table of Contents
1
UI - 9139575
AU - Ayoub JP; Valero V; Hortobagyi GN
TI -
Tamoxifen-induced female androgenetic alopecia in a patient with breast
cancer.
SO - Ann Intern Med 1997 May 1;126(9):745-6
2
UI - 11521785
AU - Icli F; Akbulut H; Dincol D; Onur H; Demirkazik A; Cam R; Cay F; Demirci
TI -
S; Uner A; Erekul S
A randomized trial of four cycles of adjuvant AC (adriamycin +
cyclophosphamide) +/- two cycles of EP (etoposide + cisplatin) in node
positive patients with breast cancer.
SO - Ann Oncol 2001 Jul;12(7):1011-3
AD - Department of Medical Oncology, Ibni Sina Hospital, Faculty of Medicine,
Ankara University, Sihhiye-Ankara, Turkey. icli@dialup.ankara.edu.tr
BACKGROUND: Four cycles of AC have been accepted as the standard
chemotherapy in breast cancer. In the present randomized study we aimed
to assess the efficacy of adjuvant etoposide + cisplatin (EP)
combination following four cycles of standard adriamycin +
cyclophosphamide (AC) in premenopausal patients with operable breast
cancer and axillary lymph node metastasis. PATIENTS AND METHODS:
Premenopausal patients with positive axillary lymph nodes following
curative modified radical mastectomy were randomized to either four
cycles of AC (82 patients) or four cycles of AC + two cycles of EP (83
patients). RESULTS: Median follow-up is 72 months. All randomized and
eligible patients are included in the analysis (AC: 80 patients, AC +
EP: 78 patients). The five-year disease-free survival (DFS) for the AC +
EP group was significantly better when compared to AC group (45.5% vs.
30.4%; P = 0.048). Again, the five-year overall survival (OS) of the
whole group was in favor of AC + EP arm, though without statistical
significance (68.6% vs. 59.1%; P = 0.247). CONCLUSION: Two cycles of EP
following four cycles of AC decreased the relapse rate in operable
breast cancer patients.
3
UI - 11521794
AU - Campone M; Fumoleau P; Delecroix V; Deporte-Fety R; Perrocheau G;
TI -
Vernillet L; Borg-Olivier O; Louboutin JP; Bissery MC; Riva A; Azli N
Phase I dose-finding and pharmacokinetic study of docetaxel and
vinorelbine as first-line chemotherapy for metastatic breast cancer.
SO - Ann Oncol 2001 Jul;12(7):909-18
AD - Centre R Gauducheau, Nantes, France.
BACKGROUND AND PURPOSE: Anthracycline-containing regimens are widely
used in advanced breast cancer. However, there is a need for new,
non-anthracycline regimens that are active in patients for whom
anthracyclines are contraindicated. The aim of this study was to
determine the maximum tolerated dose (MTD), the dose-limiting toxicities
(DLTs) and recommended doses of docetaxel and vinorelbine as first-line
chemotherapy in patients with metastatic breast cancer. The
pharmacokinetics of both drugs was also evaluated. PATIENTS AND METHODS:
Thirty-four women with first-line metastatic breast cancer were treated
with docetaxel, 60-100 mg/m2 (day 1), and vinorelbine, 20-22.5 mg/m2
(days 1 and 5), repeated every three weeks and administered on an
outpatient basis. RESULTS: Two MTDs were determined: MTD1 was defined at
the dose level using docetaxel 75 mg/m2, and vinorelbine 22.5 mg/m2 DLT
being a grade 3 stomatitis that was more related to the dose of
vinorelbine than that of docetaxel. Therefore, the study continued with
a fixed dose of vinorelbine, 20 mg/m2, and docetaxel 85-100 mg/m2. MTD2
was defined at the dose level combining docetaxel, 100 mg/m2, and
vinorelbine, 20 mg/m2; DLTs were grade 3 stomatitis and severe asthenia.
Fluid retention was observed in 41% of patients but was never severe or
a reason for patient discontinuation. In comparison with historical
experience, Daflon 500 did not seem to increase the efficacy of the
three-day corticosteroid premedication by further reducing the incidence
or severity of fluid retention. No significant neurotoxicity was
observed and no patient discontinued the study due to this site effect.
Activity was observed at all dose levels and at all metastatic sites,
with an overall response rate of 71% (95% CI: 52.0%-85.8%). The median
time to progression was 31.4 weeks (95% CI: 12-48 weeks) and median
survival was 15.6 months (95% CI: 2.6-26.6 months). The pharmacokinetics
of docetaxel and vinorelbine were not modified between day 1 and day 3
when the two drugs were combined with the day 1 administration schedule
used in this study. CONCLUSION: The recommended doses for phase II
studies are docetaxel, 75 mg/m2 (day 1), plus vinorelbine, 20 mg/m2
(days 1 and 5), repeated every three weeks. At these doses, the
combination was found to be active and well tolerated.
4
UI - 11774205
AU - Hortobagyi GN
TI -
Overview of treatment results with trastuzumab (Herceptin) in metastatic
breast cancer.
SO - Semin Oncol 2001 Dec;28(6 Suppl 18):43-7
AD - Department of Breast Medical Oncology, The University of Texas M. D.
Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030-4009,
USA.
HER2/neu amplification/overexpression confers more aggressive and
malignant characteristics on breast cancer cells. Patients with
HER2/neu-amplified breast cancer have a worse prognosis than those with
normal HER2/neu expression. Over the past decade, the intracellular
signaling pathways associated with this growth factor receptor have been
elucidated. Multiple therapeutic strategies that target the HER2/neu
oncoprotein are under development. Trastuzumab (Herceptin; Genentech,
Inc, South San Francisco, CA), a humanized monoclonal antibody that
binds to the extracellular domain of the HER2/neu receptor, has
undergone phase I, II, and III clinical trials. These studies have shown
that, as a single agent, trastuzumab has substantial and reproducible
antitumor activity in HER2/neu-amplified metastatic breast cancer. In
addition, when added to chemotherapy, trastuzumab improves antitumor
efficacy as measured by time to progression, response rate, and
survival. Additional chemotherapy/trastuzumab combinations are under
active evaluation, and new schedules of administration are being tested.
Thus, trastuzumab is the first successful example of molecularly
targeted therapy in the management of metastatic breast cancer.
Copyright 2001 by W.B. Saunders Company.
5
UI - 11815957
AU - Harris L; Batist G; Belt R; Rovira D; Navari R; Azarnia N; Welles L;
TI -
Winer E; The TLC D-99 Study Group
Liposome-encapsulated doxorubicin compared with conventional doxorubicin
in a randomized multicenter trial as first-line therapy of metastatic
breast carcinoma.
SO - Cancer 2002 Jan 1;94(1):25-36
AD - Duke University Medical Center, Durham, North Carolina, USA.
lyndsay_harris@dfci.harvard.edu
BACKGROUND: The objective of this study was to compare the efficacy and
toxicity of the liposome-encapsulated doxorubicin, TLC D-99 (Myocet,
Elan Pharmaceuticals, Princeton, NJ), and conventional doxorubicin in
first-line treatment of metastatic breast carcinoma (MBC). METHODS: Two
hundred twenty-four patients with MBC and no prior therapy for
metastatic disease were randomized to receive either TLC D-99 (75
mg/m(2)) or doxorubicin (75 mg/m(2)) every 3 weeks, in the absence of
disease progression or unacceptable toxicity. The primary efficacy
endpoint was response rate. Responses were assessed using World Health
Organization criteria and were required to be of at least 6 weeks'
duration. The primary safety endpoint was cardiotoxicity. Cardiac
function was monitored by multiple-gated radionuclide cardioangiography
scan, and the left ventricular ejection fraction (LVEF) was scored at a
central laboratory. Patients were removed from study if LVEF declined 20
or more EF units from baseline to a final value of greater than or equal
to 50%, or by 10 or more units to a final value of less than 50%, or
onset of clinical congestive heart failure (CHF). RESULTS: Median age
was 54 years in both treatment groups. All relevant prognostic factors
were balanced, with the exception that there were significantly more
progesterone receptor positive patients in the doxorubicin-treated
group. Protocol-defined cardiotoxicity was observed in 13% of TLC D-99
patients (including 2 cases of CHF) compared to 29% of doxorubicin
patients (including 9 cases of CHF). Median cumulative doxorubicin dose
at onset of cardiotoxicity was 785 mg/m(2) for TLC D-99 versus 570
mg/m(2) for doxorubicin (P = 0.0001; hazard ratio, 3.56). The overall
response rate was 26% in both treatment groups. The median TTP was 2.9
months on TLC D-99 versus 3.1 months on doxorubicin. Median survival was
16 versus 20 months with a nonsignificant trend in favor of doxorubicin
(P = 0.09). Clinical toxicities, commonly associated with doxorubicin,
appeared less common with TLC D-99, although the difference was not
statistically significant. There was only one report of palmar-plantar
erythrodysesthesia (Grade 2) with this liposomal formulation of
doxorubicin. CONCLUSIONS: Single-agent TLC D-99 produces less
cardiotoxicity than doxorubicin, while providing comparable antitumor
activity. Copyright 2002 American Cancer Society.
6
UI - 11816465
AU - Kitahara S; Ogata H; Katagiri T; Nonaka K; Shiba T
TI -
[A 5'-DFUR + CPA + THP therapy that was effective for
paclitaxel-refractory pulmonary metastasis of breast cancer--a case
report]
SO - Gan To Kagaku Ryoho 2002 Jan;29(1):111-4
AD - Second Dept. of Surgery, School of Medicine, Toho University.
What should be the standard treatment for taxane-refractory metastatic
breast cancer remains controversial. In this paper, a case in which the
5'-DFUR + CPA + THP therapy was effective for paclitaxel-refractory
metastatic breast cancer is reported. A 41-year-old female received
pectoral muscle preserved mastectomy under diagnosis of the left breast
found in the left middle lung field with chest X-ray. Paclitaxel 210
mg/m2 (once for three weeks, 8 cycles in total) resulted in marked
improvement. The regimen of paclitaxel 70 mg/m2 (medication consecutive
once-weekly for three weeks, and withdrawal for next week; 1 cycle) was
carried out continuously with the patient ambulatory. Because resistance
to the treatment appeared at the time the total dose reached 2,700 mg,
5'-DFUR + CPA + THP therapy (THP 30 mg/m2 (i.v.) x day 1, CPA 77 mg/m2
(p.o.) x 14 days, 5'-DFUR 460 mg/m2 (p.o.) x 14 days; 3 weeks with 1
cycle) was carried out, and definite improvement in the lung findings
were observed. 5'-DFUR + CPA + THP therapy may be of use as a
second-line therapy in paclitaxel-refractory recurrent breast cancer.
7
UI - 11816466
AU - Sakuta M; Sumiyama Y; Okamoto Y; Noto Y; Naka I; Kiribayashi T
TI -
[A case of locally recurrent breast cancer in which phlebothrombosis of
the right leg after hormonal therapy using a high dose of toremifene
citrate]
SO - Gan To Kagaku Ryoho 2002 Jan;29(1):115-8
AD - Third Dept. of Surgery, Toho University School of Medicine.
A 72-year-old female had undergone mastectomy at the age of 67 for right
breast cancer (T2a, n1 alpha, positive for ER). In the surgery the
pectoralis muscle was preserved. For adjuvant therapy, 20 mg/day of
tamoxifen was orally administered for 5 years. Six years after surgery,
relapse was detected in the right major pectoralis muscle. Irradiation
at this site and oral administration of 120 mg/day of toremifene citrate
were started. The patient had a medical history of diabetes, and the
control of her blood sugar was poor. About 2 months after oral
administration of toremifene citrate was started, flares with blebs and
swelling were observed in the right lower leg, suggesting acute
phlebothrombosis of the right lower limb. The symptoms were ameliorated
by intravenous administration of heparin and an antibiotic. In
administering a high dose of toremifene citrate to patients with
complications, careful follow-up is needed.
8
UI - 11816478
AU - Kuroi K; Tanaka C; Bando H; Saji S; Hayashi K; Toi M
TI -
[Efficacy of biweekly paclitaxel therapy in advanced or recurrent breast
cancer]
SO - Gan To Kagaku Ryoho 2002 Jan;29(1):55-60
AD - Dept. of Surgery, Tokyo Metropolitan Komagome Hospital.
To evaluate the feasibility and efficacy of a biweekly schedule of
paclitaxel in advanced or recurrent breast cancer, 18 patients were
enrolled in this pilot study. Paclitaxel of 120 mg/m2 was administered
over 3 hours, and cycles were repeated every two weeks until disease
progression or toxicity precluded further treatment. Patients received a
median of 10 infusions with actual dose intensity of 55.9 mg/m2/wk, and
median time to progression was 4.8 months. The overall response rate was
33.3%, and one patient achieved stable disease for at least 6 months.
The responders included patients who received prior anthracycline and/or
docetaxel treatment, and the response rate was consistent regardless of
metastatic sites. Myelosuppression was the most common toxicity, and a
few patients needed G-CSF support, treatment delay or dose reduction
because of grade 3 or 4 neutropenia or leukopenia. Although one patient
withdrew from this study because of grade 3 sensory disturbance, this
regimen was generally well tolerated. A biweekly schedule of paclitaxel
seems to be feasible and effective in patients with advanced or
recurrent breast cancer.
9
UI - 11078487
AU - Bonneterre J; Thurlimann B; Robertson JF; Krzakowski M; Mauriac L;
TI -
Koralewski P; Vergote I; Webster A; Steinberg M; von Euler M
Anastrozole versus tamoxifen as first-line therapy for advanced breast
cancer in 668 postmenopausal women: results of the Tamoxifen or Arimidex
Randomized Group Efficacy and Tolerability study.
SO - J Clin Oncol 2000 Nov 15;18(22):3748-57
AD - Centre Oscar Lambret, Lille, France. j-bonneterre@o-lambret.fr
PURPOSE: To compare the efficacy and tolerability of anastrozole
(Arimidex; AstraZeneca, Wilmington, DE, and Macclesfield, United
Kingdom) with that of tamoxifen as first-line therapy for advanced
breast cancer (ABC) in postmenopausal women. PATIENTS AND METHODS: This
randomized, double-blind, multicenter study evaluated the efficacy of
anastrozole 1 mg once daily relative to tamoxifen 20 mg once daily in
patients with tumors that were hormone receptor-positive or of unknown
receptor status who were eligible for endocrine therapy. The primary end
points were time to progression (TTP), objective response (OR), and
tolerability. RESULTS: A total of 668 patients (340 in the anastrozole
arm and 328 in the tamoxifen arm) were randomized to treatment and
followed-up for a median of 19 months. Median TTP was similar for both
treatments (8.2 months in patients who received anastrozole and 8.3
months in patients who received tamoxifen). The tamoxifen:anastrozole
hazards ratio was 0.99 (lower one-sided 95% confidence limit, 0.86),
demonstrating that anastrozole was at least equivalent to tamoxifen.
Anastrozole was also as effective as tamoxifen in terms of OR (32.9% of
anastrozole and 32.6% of tamoxifen patients achieved a complete response
[CR] or partial response [PR]). Clinical benefit (CR + PR +
stabilization of > or = 24 weeks) rates were 56.2% and 55.5% for
patients receiving anastrozole and tamoxifen, respectively. Both
treatments were well tolerated. However, incidences of thromboembolic
events and vaginal bleeding were reported in fewer patients treated with
anastrozole than with tamoxifen (4.8% v 7.3% [thromboembolic events] and
1.2% v 2.4% [vaginal bleeding], respectively). CONCLUSION: Anastrozole
satisfied the predefined criteria for equivalence to tamoxifen. Together
with the lower observed incidence of thromboembolic events and vaginal
bleeding, these findings indicate that anastrozole should be considered
as first-line therapy for postmenopausal women with ABC.
10
UI - 11078488
AU - Nabholtz JM; Buzdar A; Pollak M; Harwin W; Burton G; Mangalik A;
TI -
Steinberg M; Webster A; von Euler M
Anastrozole is superior to tamoxifen as first-line therapy for advanced
breast cancer in postmenopausal women: results of a North American
multicenter randomized trial. Arimidex Study Group.
SO - J Clin Oncol 2000 Nov 15;18(22):3758-67
AD - Cancer-Cross Institute, Edmonton, Alberta, Canada.
jean-marc.nabholtz@bcom
PURPOSE: The efficacy and tolerability of anastrozole (Arimidex;
AstraZeneca, Wilmington, DE, and Macclesfield, United Kingdom) and
tamoxifen were compared as first-line therapy for advanced breast cancer
in 353 postmenopausal women. PATIENTS AND METHODS: The randomized,
double-blind, multicenter study was designed to evaluate anastrozole 1
mg once daily relative to tamoxifen 20 mg once daily in patients with
hormone receptor-positive tumors or tumors of unknown receptor status
who were eligible for endocrine therapy. Primary end points were
objective response (OR), defined as complete (CR) or partial (PR)
response, time to progression (TTP), and tolerability. RESULTS:
Anastrozole was as effective as tamoxifen in terms of OR (21% v 17% of
patients, respectively), with clinical benefit (CR + PR + stabilization
> or = 24 weeks) observed in 59% of patients on anastrozole and 46% on
tamoxifen (two-sided P =.0098, retrospective analysis). Anastrozole had
a significant advantage over tamoxifen in terms of TTP (median TTP of
11.1 and 5.6 months for anastrozole and tamoxifen, respectively;
two-sided P =.005). The tamoxifen:anastrozole hazards ratio was 1.44
(lower one-sided 95% confidence limit, 1.16). Both treatments were well
tolerated. However, thromboembolic events and vaginal bleeding were
reported in fewer patients who received anastrozole compared with those
who received tamoxifen (4.1% v 8.2% [thromboembolic events] and 1.2% v
3.8% [vaginal bleeding], respectively). CONCLUSION: Anastrozole
satisfied the predefined criteria for equivalence to tamoxifen.
Furthermore, we observed both a significant increase in TTP and a lower
incidence of thromboembolic events and vaginal bleeding with
anastrozole. These findings indicate that anastrozole should be
considered as first-line therapy for postmenopausal women with advanced
breast cancer.
11
UI - 11331343
AU - Copur MS; Ledakis P; Bolton M; Norvell M; Muhvic J
TI -
Is anastrozole superior to tamoxifen as first-line therapy for advanced
breast cancer?
SO - J Clin Oncol 2001 May 1;19(9):2578; discussion 2580-2
12
UI - 11525361
AU - Le Moal G; Paccalin M; Breux JP; Roblot F; Roblot P; Becq-Giraudon B
TI -
Central venous catheter-related infection due to Comamonas testosteroni
in a woman with breast cancer.
SO - Scand J Infect Dis 2001;33(8):627-8
AD - Department of Internal Medicine and Infectious Diseases, CHU La
Miletrie, Poitiers, France.
A 75-y-old woman with breast cancer presented with bacteremia due to
Comamonas testosteroni. Evolution was favorable following adapted
antimicrobial therapy and removal of a central venous catheter. This
germ seems to be a rare pathogen; as reported in the literature, it is
mostly encountered in patients with predisposing factors.
13
UI - 11464976
AU - Schneeweiss A; Goerner R; Hensel MA; Lauschner I; Sinn P; Kaul S; Egerer
TI -
G; Beldermann F; Geberth M; Solomayer E; Grischke EM; Haas R; Ho AD;
Bastert G
Tandem high-dose chemotherapy in high-risk primary breast cancer: a
multivariate analysis and a matched-pair comparison with standard-dose
chemotherapy.
SO - Biol Blood Marrow Transplant 2001;7(6):332-42
AD - Department of Gynecology and Obstetrics, University of Heidelberg,
Germany. andreas_schneeweis@med.uni-heidelberg.de
Stem cell-supported high-dose chemotherapy (HDCT) is currently being
evaluated in patients with high-risk primary breast cancer (HRPBC), as
defined by extensive axillary lymph node involvement. Conclusive results
from randomized studies with sufficient patient numbers and follow-up
are pending. We retrospectively analyzed 144 HRPBC patients enrolled in
a single-arm trial of tandem HDCT at the University of Heidelberg to
evaluate the prognostic value of nodal ratio, HER2/neu status, and
cytokeratin-positive bone marrow cells and to compare the outcomes of
these patients with those of a conventionally treated control group of
91 patients matched by nodal ratio, tumor size, combined
hormone-receptor status, and HER2/neu status. The tandem HDCT regimen
consisted of 2 cycles of induction chemotherapy followed by 2 cycles of
blood stem cell-supported high-dose ifosfamide, 12 g/m2; carboplatin,
900 mg/M2; and epirubicin, 180 mg/m2. Conventionally treated patients
received a regimen containing anthracycline without taxanes (52
patients) or CMF (cyclophosphamide, methotrexate, and 5-flurouracil; 39
patients). With a median follow-up of 3.8 years, disease-free, distant
disease-free, and overall survival rates were 62%, 65%, and 84%,
respectively. In univariate analysis, besides the hormone receptor
status (P = .007), HER2/neu overexpression was the strongest predictor
of earlier death (P = .017). In multivariate analysis, a nodal ratio of
> or =0.8 was found to be the only independent predictor of relapse
(relative risk [RR] = 2.09; 95% confidence interval [CI], 1.21-3.60; P =
.008) and only the absence of hormone receptors was associated with
earlier death (RR = 3.59; 95% CI, 1.45-8.86; P = .006). Despite a trend
toward later distant relapse after HDCT compared with standard-dose
chemotherapy with a median follow-up of 3 years (P = .059), thus far,
matched-pair analysis has not demonstrated significantly better survival
rates after HDCT in all matched patients (P = .786) or in the subgroups
of anthracycline-treated patients and patients with and without
overexpression of HER2/neu. So far, the follow-up time has been too
short to draw definite conclusions; however, patients with a nodal ratio
of > or =0.8, receptor-negative tumors, or HER2/neu overexpression are
at high risk for relapse and death, irrespective of the kind of adjuvant
chemotherapy.
14
UI - 11716446
AU - Tominaga T; Sano M; Nishi T; Sasaki M; Yoshida K; Kimura M; Takashima S;
TI -
Asano T; Yoshida M; Fujiwara J; Danno M
Postoperative chemoendocrine therapy for women with node-positive stage
II breast cancer with combined cyclophosphamide, tamoxifen, and
1-hexylcarbamoyl-5-fluorouracil.
SO - Eur J Surg 2001 Aug;167(8):598-604
AD - Department of Surgery, Tokyo Metropolitan Komagome Hospital, Japan.
OBJECTIVE: To find out whether the addition of
1-hexylcarbamoyl-5-fluorouracil to a postoperative regimen of oral
cyclophosphamide and tamoxifen improved the prognosis of carcinoma of
the breast. DESIGN: Randomised controlled clinical trial. SETTING: 127
Institutions in Japan. SUBJECTS: 785 Patients with stage II carcinoma
(palpable axillary nodes) who had total mastectomy and axillary
clearance. INTERVENTIONS: The control group were given oral
cyclophosphamide 50 mg/day and tamoxifen 20 mg/day for 2 years; the
experimental group were given these drugs plus
1-hexylcarbamoyl-5-fluorouracil 300 mg/day for 2 years. RESULTS: There
was no survival advantage (and more toxicity) in the experimental group,
except in a subgroup with 1-3 axillary nodes involved. CONCLUSION: The
advantage of triple chemotherapy in the subgroup must be substantiated
by a new randomised trial confined to patients with 1-3 axillary nodes
involved.
15
UI - 11791116
AU - Bentrem DJ; O'Regan RM; Jordan VC
TI -
New strategies for the treatment of breast cancer.
SO - Breast Cancer 2001;8(4):265-74
AD - Department of Surgery, Robert H. Lurie Comprehensive Cancer Center,
Northwestern University Medical School, Chicago, IL 60611, USA.
16
UI - 11791121
AU - Abrams JS
TI -
Adjuvant therapy for breast cancer--results from the USA consensus
conference.
SO - Breast Cancer 2001;8(4):298-304
AD - Clinical Investigations Branch, Cancer Therapy Evaluation Program,
Division of Cancer Treatment and Diagnosis, National Cancer Institute,
National Institutes of Health, 6130 Executive Boulevard, EPN 7040,
Rockville, MD 20852, USA.
The National Institutes of Health, USA sponsored a Consensus Development
Conference on November 1-3, 2000 to review several major questions
regarding the adjuvant treatment of breast cancer. A non-governmental
group of oncology experts was selected to review clinical trial data and
judge the evidence presented by 33 breast cancer researchers. Their
conclusions resulted in the following recommendations: (1) Prognostic
factors critical for determining risk of recurrence are age, axillary
lymph node status, tumor size, histologic type and grade and hormone
receptor status. (2) Tamoxifen, administered for 5 years, significantly
improves long-term survival for women of all age groups with hormone
receptor-positive tumors. Ovarian ablation also prolongs survival in
premenopausal women. (3) Multi-agent chemotherapy of 4-6 months duration
is associated with an improvement in survival in both hormone
receptor-positive and -negative tumors. Anthracycline-containing
regimens offer the greatest survival advantage. The role of taxanes is
uncertain but they may be useful in selected patients with node-positive
tumors. Women with small, node-negative tumors, women over age 70, and
those with tumors of favorable histologic subtype (mucinous or tubular)
may not require chemotherapy. (4) Adjuvant radiotherapy to the regional
lymph nodes and chest wall following mastectomy is indicated for women
with 4 or more axillary nodes. (5) Physicians should employ effective
visual aids to help them present a complete and balanced view of the
absolute benefits versus the side-effects of adjuvant treatments.
Important avenues of future research were also discussed and suggestions
were made.
17
UI - 11791122
AU - Nabholtz JM; Reese DM
TI -
Third-generation aromatase inhibitors in the treatment of advanced
breast cancer.
SO - Breast Cancer 2001;8(4):305-9
AD - Cancer Therapy Development Program and Jonsson Comprehensive Cancer
Center, University of California, Los Angeles, Peter Ueberroth Building
3360B, 10945 Le Conte Avenue, Los Angeles, CA 90095-7077, USA.
jean-marc.nabholtz@bcirg.com
18
UI - 11791123
AU - Tokuda Y; Suzuki Y; Ohta M; Saito Y; Kubota M; Tajima T; Umemura S;
TI -
Osamura RY
Compassionate use of humanized anti-HER2/neu protein, trastuzumab for
metastatic breast cancer in Japan.
SO - Breast Cancer 2001;8(4):310-5
AD - Department of Surgery, Tokai University School of Medicine, Bohseidai,
Isehara, Kanagawa 259-1193, Japan. tokuda@is.icc.u-tokai.ac.jp
The HER-2/neu protein is thought to be a unique and useful target for
antibody therapy of cancers overexpressing the HER-2/neu gene. The
recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab
(Herceptin) was approved for clinical use in the US in 1998. In Japan,
it was approved and later became available in June, 2001. We have
treated 41 patients with metastatic breast cancer with trastuzumab
purchased from the US. In this paper, the details of the patients we
experienced are reviewed.
19
UI - 11791124
AU - Umemura S; Sakamoto G; Sasano H; Tsuda H; Akiyama F; Kurosumi M; Tokuda
TI -
Y; Watanabe T; Toi M; Hasegawa T; Osamura RY
Evaluation of HER2 status: for the treatment of metastatic breast
cancers by humanized anti-HER2 Monoclonal antibody (trastuzumab)
(Pathological committee for optimal use of trastuzumab).
SO - Breast Cancer 2001;8(4):316-20
AD - Department of Pathology, Tokai University School of Medicine, Isehara,
259-1193, Japan.
For the treatment of patients with metastatic breast cancer by humanized
anti- human epidermal growth factor receptor type 2 (HER2) antibody
(trastuzumab), it is important to evaluate HER2 status adequately. "A
guideline for HER2 testing" and "HER2 atlas" produced by the
"Pathological committee for optimal use of trastuzumab" are introduced
in this report. Appropriate evaluations of biological markers are
essential for targeting therapy.
20
UI - 11791125
AU - Gluck S
TI -
The worldwide perspective in the adjuvant treatment of primary lymph
node positive breast cancer.
SO - Breast Cancer 2001;8(4):321-8
AD - Department of Oncology, University of Calgary, AB, Canada.
gluck@ucalgary.ca
Adjuvant treatment of early breast cancer has experienced major changes
in the last 25 years. Since the mid 1970s when cyclophosphamide,
methotrexate and 5-fluorouracil (CMF) resulted in statistically
significant and clinically meaningful improvements in disease-free and
overall survival, the use of adjuvant chemotherapy has become common
practice worldwide. Anthracyclines have long been considered to be among
the most active available agents to treat breast cancer and they have
become a core component of adjuvant regimens. Anthracycline-containing
polychemotherapy regimens provide a significant benefit over CMF.
Regimens containing epirubicin are associated with a significant
prolongation in relapse-free and overall survival rates compared with
standard therapies including CMF. Epirubicin-taxane combinations are
highly active in treating metastatic breast cancer and do not appear to
be associated with any pharmacokinetic interactions. Epirubicin is a
unique anthracycline whose introduction to the US market represents a
significant advance in breast cancer treatment. Ongoing research efforts
are focusing on combining anthracyclines with taxanes in an effort to
continue to improve outcomes following adjuvant therapy.
21
UI - 11791126
AU - Toi M; Bando H; Saji S
TI -
Aromatase and aromatase inhibitors.
SO - Breast Cancer 2001;8(4):329-32
AD - Tokyo Metropolitan Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku,
Tokyo 113, Japan. maktoi77@wa2.so-net.ne.jp
Aromatase inhibition provides both paracrine/intracrine and endocrine
treatment. Recent accumulated data clarified that 3rd generation
aromatase inhibitors potently suppress intratumoral estrogen synthesis
particularly in postmenopausal patients. In the 2nd-line treatment for
metastatic breast cancer patients, aromatase inhibitors achieved results
antitumor activity at least equal to and sometimes better than that of
tamoxifen. In the first-line treatment for metastatic breast cancer
patients, a recent pivotal study clearly demonstrated that aromatase
inhibitor was superior to tamoxifen. Based upon these results, various
adjuvant trials which compare aromatase inhibitors with tamoxifen and
attempt to determine optimal combination therapies and treatment periods
with aromatase inhibitors are currently being conducted. In addition,
preliminary studies conducted in neoadjuvant setting indicated that
aromatase inhibitors showed an extremely high response rate, which
predicts a future paradigm, that neoadjuvant therapy using aromatase
inhibitors singly or in combination may become standard for
hormone-responsive and post-menopausal breast cancer patients.
22
UI - 11791127
AU - Kubota T; Furukawa T; Tanino H; Suto A; Otan Y; Watanabe M; Ikeda T;
TI -
Kitajima M
Resistant mechanisms of anthracyclines--pirarubicin might partly break
through the P-glycoprotein-mediated drug-resistance of human breast
cancer tissues.
SO - Breast Cancer 2001;8(4):333-8
AD - Department of Surgery, School of Medicine, Keio University, 35
Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
tkubota@sc.itc.keio.ac.jp
Juliano and Ling initially reported the expression of a 170 kDa
glycoprotein in the membrane of Chinese hamster ovarian cells in 1976,
and named this glycoprotein P-glycoprotein (P-gp) based on its predicted
role of causing "permeability" of the cell membrane. After much research
on anthracycline-resistance, this P-gp was finally characterized as a
multidrug-resistant protein coded by the mdr1 gene. Multidrug resistance
associated protein (MRP) was initially cloned from H69AR, a human small
cell-lung carcinoma cell line which is resistant to doxorubicin (DXR)
but does not express P-gp. MRP also excretes substrates through the cell
membrane using energy from ATP catabolism. The substrate of MRP is
conjugated with glutathione before active efflux from cell membrane.
Recently, membrane transporter proteins were re-categorized as members
of "ATP-Binding Cassette transporter"(ABC-transporter) superfamily, as
shown at http://www.med.rug.nl/mdl/humanabc.htm and
http://www.gene.ucl.ac.uk/nomenclature/genefamily/abc.html. A total of
ABC transporters have been defined, and MDR1 and multidrug resistance
associated protein 1 (MRP1) were reclassified as ABCB1 and ABCC1,
respectively. Their associated superfamilies include 11 and 13 other
protein, in addition to ABCB and ABCC, respectively. Lung
resistance-related protein (LRP) is not a member of the superfamily of
ABC transporter proteins, because it shows nuclear membrane expression
and transports substrate between nucleus and cytoplasm. LRP was
initially cloned from a non-small cell lung carcinoma cell line,
SW1573/2R120 which is resistant to DXR, vincristine, etoposide and
gramicidin D and does not express P-gp. The mechanisms of resistance
remains unclear, and why some resistant cell lines express P-gp and
others express MRP and/or LRP is likewise unclear.
23
UI - 11791128
AU - Heys SD
TI -
Evolution of breast cancer management: focus on neoadjuvant
chemotherapy.
SO - Breast Cancer 2001;8(4):339-50
AD - Section of Surgical Oncology, Department of Surgery, and the Aberdeen
Breast Unit, University Medical Buildings, University of Aberdeen,
Foresterhill, Aberdeen AB9 2ZD, Scotland, UK. s.d.heys@abdn.ac.uk
24
UI - 11791129
AU - Nakamura S; Kenjo H; Nishio T; Kazama T; Do O; Suzuki K
TI -
3D-MR mammography-guided breast conserving surgery after neoadjuvant
chemotherapy: clinical results and future perspectives with reference to
FDG-PET.
SO - Breast Cancer 2001;8(4):351-4
AD - Department of Surgery, St. Luke's International Hospital, 9-1
Akashi-cho, Chuo-ku, Tokyo 104-0044, Japan. seigonak@po.iijnet.or.jp
BACKGROUNDS: Three dimensional MR Mammography (3D-MRM) can detect tumor
extension more accurately than mammography or ultrasound. There are two
shrinkage patterns observed by 3D-MRM after neoadjuvant chemotherapy.
Concentric shrinkage is a good indication for breast conserving surgery.
On the other hand, a dendritic pattern was represent ductal spread.
Therefore, we developed MRM guided mapping to aid BCS for tumors showing
a dendritic pattern. METHODS: Fifteen patients consisting of 8 stage II
(T > 3.5 cm) cases and 7 stage IIIa cases aged 39 to 61 years (mean 47-8
years) were treated with AT neoadjuvant chemotherapy with the aim of
performing breast conserving surgery. All patients were examined by
3D-MRM before and after neoadjuvant chemotherapy. Breast conserving
surgery indications were determined by tumor volume reduction and
shrinkage patterns on 3D-MRM. Supine position mapping using MRM was
performed for dendritic type tumors. FDG-PET was simultaneously
performed for one case with bilateral breast cancer. RESULTS: Breast
conserving surgery was performed for 13 of the 15 cases. One case
underwent re-operating and mastectomy because of a positive margin. One
case had microscopically positive margin and received boost radiation.
Therefore, 11 of 15 cases (73.3%) underwent BCS and achieved negative
margins under MRM guidance. PET scanning can detect residual tumor and
occult metastasis but it is not suitable for mapping because of its
spatial resolution. Conclusions: 3D-MRM is a useful modality to select
appropriate cases for breast conserving surgery after neoadjuvant
chemotherapy. FDG-PET can also detect residual tumor or occult
metastasis but it may not be suitable for mapping. Because both
examinations have potential, further evaluation of their clinical
efficacy is necessary.
25
UI - 11677975
AU - Pocard M; Vincent-Salomon A; Girodet J; Salmon RJ
TI -
Effects of preoperative chemotherapy on liver function tests after
hepatectomy.
SO - Hepatogastroenterology 2001 Sep-Oct;48(41):1406-8
AD - Service de Chirurgie Generale et Digestive, Hopital Lariboisiere 2 rue
Ambroise Pare, 75475 Paris, France. marc.pocard@sat.ap-hop-paris.fr
BACKGROUND/AIMS: Surgical resection of liver metastases is performed
increasingly frequently after chemotherapy, which can induce fatty
degeneration, possibly modifying the postoperative course after
hepatectomy. This study evaluated the effect of chemotherapy on
postoperative liver function tests according to the use of preoperative
chemotherapy or not. METHODOLOGY: Thirty-two patients were operated on
for isolated breast cancer hepatic metastases, after stabilization or
complete response to systemic therapy. The first group included 20
patients operated on after chemotherapy (9 major and 11 minor hepatic
resections). The second group included 12 patients operated on without
chemotherapy (3 major and 9 minor hepatic resections). RESULTS:
Histological examination after chemotherapy confirmed micronodular fatty
degeneration in 85% of cases, versus none in the control group (P =
0.05). Fall in prothrombin time on day 1 (D1) was more marked in the
chemotherapy group (58%) versus control group (74%) (P = 0.001).
gamma-glutamyl transpeptidase did not rise on D7 in the chemotherapy
group (1.4 x N), even after major hepatectomy (1.6 x N), in contrast
with the control group, in which the mean gamma-glutamyl transpeptidase
on D7 was 4.6 x N after major hepatectomy and 2 x N after minor
hepatectomy (P = 0.05). CONCLUSIONS: Chemotherapy induces almost
constant fatty degeneration of the liver. Hepatic regeneration in the
postchemotherapy liver is delayed, as reflected by a later and lower
elevation of gamma-glutamyl transpeptidase. The predictive risk of liver
failure, reflected by prothrombin time, following minor hepatectomy on
postchemotherapy liver is similar to that of major hepatectomy to
healthy liver.
26
UI - 11693900
AU - Buchholz TA; Hill BS; Tucker SL; Frye DK; Kuerer HM; Buzdar AU; McNeese
TI -
MD; Singletary SE; Ueno NT; Pusztai L; Valero V; Hortobagyi GN
Factors predictive of outcome in patients with breast cancer refractory
to neoadjuvant chemotherapy.
SO - Cancer J 2001 Sep-Oct;7(5):413-20
AD - Department of Radiation Oncology,The University of Texas M.D. Anderson
Cancer Center, Houston 77030, USA.
PURPOSE: The purpose of this study was to determine the clinical,
pathological, and treatment factors that are predictive of
local-regional recurrence and overall survival for patients with breast
cancer that is refractory to neoadjuvant chemotherapy. PATIENTS AND
METHODS: This study analyzed the data of the 177 breast cancer patients
treated on our institutional protocols who had less than a partial
response to neoadjuvant chemotherapy. The initial clinical stage of
disease was II in 27%, III in 69%, and IV (supraclavicular lymph node
involvement) in 4%. Surgery was performed in 94% of the patients, and
77% of these patients also received adjuvant chemotherapy. RESULTS:
After a median follow-up of 5.2 years, 106 patients experienced disease
recurrence, with 98 of these having distant metastases and 45 having
local-regional recurrence. The 5- and 10-year overall survivals for the
entire group were 56% and 33%, respectively. The factors that were
independently associated with a statistically significant poorer overall
survival in a Cox regression analysis were pathologically involved lymph
nodes after surgery, estrogen receptor-negative disease, and progressive
disease during neoadjuvant chemotherapy. The 5-year overall survival for
patients with pathologically negative lymph nodes ranged from 84%
(estrogen receptor-positive disease) to 75% (estrogen re-ceptor-negative
disease), compared with rates for patients with pathologically positive
lymph nodes of 66% (estrogen receptor-positive disease) and 40%
(estrogen receptor-negative disease). The 5-year survival of patients
with progressive disease was only 19%. The 5- and 10-year local-regional
recurrence rates for the 177 patients were 27% and 34%, respectively.
Significant factors on Cox analysis that predicted for local-regional
recurrence were four or more pathologically involved lymph nodes and
estrogen receptor-negative disease. For the 105 patients treated with
surgery and postoperative radiation therapy, the 10-year local-regional
recurrence rates for the subgroups with 0, 1, or 2 of these factors were
12%, 25%, and 44%, respectively. CONCLUSIONS: For patients with a poor
response to neoadjuvant chemotherapy, conventional treatments achieve
reasonable outcomes in those with lymph node-negative disease or
estrogen receptor-positive disease. However, more active systemic and
local therapies are needed for patients with estrogen receptor-negative
disease and positive lymph nodes and for those with clinical evidence of
progressive disease during neoadjuvant chemotherapy.
27
UI - 11782394
AU - Crawford KW; Bowen WD
TI -
Sigma-2 receptor agonists activate a novel apoptotic pathway and
potentiate antineoplastic drugs in breast tumor cell lines.
SO - Cancer Res 2002 Jan 1;62(1):313-22
AD - Howard University College of Medicine, Department of Pharmacology,
Washington, DC 20059, USA.
We have reported previously that sigma-2 receptors are expressed in high
densities in a variety of tumor cell types (B. J. Vilner et al., Cancer
Res., 55: 408-413, 1995) and that various sigma ligands have cytotoxic
effects (B. J. Vilner et al., J. Neurosci., 15: 117-134, 1995). Other
investigators have demonstrated increased expression of sigma-2
receptors in rapidly proliferating tumors (R. H. Mach et al., Cancer
Res., 57: 156-161, 1997) and the ability of some sigma ligands to
inhibit proliferation (P. J. Brent and G. T. Pang, Eur. J. Pharmacol.,
278: 151-160, 1995). We demonstrate here the ability of sigma-2 receptor
agonists to induce cell death by a mechanism consistent with apoptosis.
In breast tumor cell lines that are sensitive (MCF-7) and resistant
(MCF-7/Adr-, T47D, and SKBr3) to antineoplastic agents, incubation with
the sigma-2 subtype-selective agonists CB-64D and CB-184 produced
dose-dependent cytotoxicity (measured by lactate dehydrogenase release
into medium). The EC(50) for this response was similar across cell
lines, irrespective of p53 genotype and drug-resistance phenotype.
CB-64D and the subtype nonselective sigma-2 agonists haloperidol and
reduced haloperidol induced terminal deoxynucleotidyl
transferase-mediated dUTP nick end labeling staining in MCF-7 and T47D
cells, indicating that cell death occurs via apoptosis. Apoptosis was
also indicated by increases in Annexin V binding caused by CB-64D. In
MCF-7 cells, cytotoxicity and Annexin V binding induced by the
antineoplastics doxorubicin and actinomycin D was partially or
completely abrogated by certain specific and general inhibitors of
caspases. In contrast, caspase inhibitors had no effect on sigma-2
receptor-mediated (CB-64D and CB-184) cytotoxicity or Annexin V binding.
Marked potentiation of cytotoxicity was observed when a subtoxic dose of
CB-184 was combined with doxorubicin or actinomycin D, both in
drug-sensitive (MCF-7) and drug-resistant (MCF-7/Adr-) cell lines.
Haloperidol potentiated doxorubicin only in drug-resistant cells. These
findings suggest the involvement of a novel p53- and caspase-independent
apoptotic pathway used by sigma-2 receptors, which is distinct from
mechanisms used by some DNA-damaging, antineoplastic agents and other
apoptotic stimuli. These observations further suggest that sigma-2
receptors may be targets that can be therapeutically exploited in the
treatment of both drug-sensitive and drug-resistant metastatic tumors.
28
UI - 11718178
AU - Anonymous
TI -
Exemestane: new preparation. No tangible advance in metastatic breast
cancer after tamoxifen failure.
SO - Prescrire Int 2001 Aug;10(54):108-9
(1) The reference second-line hormone treatment for breast cancer in
postmenopausal women, after failure of anti-oestrogen therapy, is an
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