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Abramson Cancer CenterNCI CANCERLIT® Search: Chemotherapy for Breast Cancer - June 2002
National Cancer Institute®
Last Modified: June 1, 2002
- Standard medical treatment for early breast cancer.
- Utilization of sentinel lymph node mapping to determine pathologic outcomes for patients receiving neoadjuvant chemotherapy for locally
- A prospective trial of preoperative chemotherapy in resectable breast cancer: predictors of breast-conservation therapy feasibility.
- Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast cancer may reliably represent the axilla except for inflammatory breast
- Analysis of sentinel lymph node mapping with immediate pathologic review in patients receiving preoperative chemotherapy for breast carcinoma.
- Tamoxifen as the primary treatment in elderly patients with breast cancer.
- The limits of tamoxifen.
- Phase II study of oxaliplatin and fluorouracil in taxane- and anthracycline-pretreated breast cancer patients.
- Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese and Chinese women with operable breast cancer.
- Tamoxifen resistant and refractory breast cancer: the value of aromatase inhibitors.
- Upstaging tamoxifen? New classes of drugs emerging for breast cancer.
- Antiaromatase agents: evolving role in adjuvant therapy.
- Benefits of epoetin alfa in anemic breast cancer patients receiving chemotherapy.
- Biochemical effects and growth inhibition in MCF-7 cells caused by novel sulphonamido oxa-polyamine derivatives.
- ICI 182,780 (Fulvestrant)--the first oestrogen receptor down-regulator--current clinical data.
- Anastrozole (Arimidex)--an aromatase inhibitor for the adjuvant setting?
- T-cell dynamics after high-dose chemotherapy in adults: elucidation of the elusive CD8+ subset reveals multiple homeostatic T-cell compartments
- Randomised, phase II trial comparing oral capecitabine (Xeloda) with paclitaxel in patients with metastatic/advanced breast cancer pretreated
- Effect of all-trans-retinoic acid on the hypercoagulable state of patients with breast cancer.
- [Incidence of emesis in outpatients on chemotherapy for breast cancer and the clinical efficacy of ondansetron hydrochloride tablets]
- [CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study for postmenopausal women with advanced or recurrent breast cancer (no.
- [CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study in postmenopausal women with advanced or recurrent breast cancer (no.
- [A case of breast cancer with multiple bone metastases that responded remarkably to doxifluridine (5'-DFUR), cyclophosphamide (CPA),
- Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer.
- Preoperative/neoadjuvant medical therapy for early breast cancer.
- Optimum anthracycline-based chemotherapy for early breast cancer.
- HER2 status in patients with breast carcinoma is not modified selectively by preoperative chemotherapy and is stable during the
- A comparison of liposomal formulations of doxorubicin with drug administered in free form: changing toxicity profiles.
- Prognostic value of TP53 gene mutation in adjuvant treated breast cancer patients.
- Acquisition of multidrug resistance in recurrent breast cancer demonstrated by the histoculture drug response assay.
- Tamoxifen for the treatment and prevention of breast cancer: an update.
- The expanding role of epirubicin in the treatment of breast cancer.
- Anti-aromatase agents in the treatment and prevention of breast cancer.
- Endocrine and clinical endpoints of exemestane as neoadjuvant therapy.
- Phase I study of eniluracil and oral 5-fluorouracil in combination with docetaxel in the treatment of patients with metastatic breast carcinoma.
- Phase I/II study of gemcitabine in association with vinorelbine for metastatic breast cancer.
- [The use of adjuvant chemotherapy in stage II breast cancer in the last 25 years--a brief review]
- Bisphosphonates in the treatment of metastatic breast cancer.
- Comparative study of tropisetron with the addition of dexamethasone or alprazolam in breast cancer patients receiving adjuvant chemotherapy
- Pemetrexed: a promising new treatment for breast cancer.
- Raloxifene is associated with less side effects than tamoxifen in women with early breast cancer: a questionnaire study from one physician's
- Our experience with chemotherapeutic agents in the treatment of breast cancer.
- Can we select which patients with small breast cancers should receive adjuvant chemotherapy?
- Start tamoxifen after completing chemotherapy, US researchers say.
- Adjuvant tamoxifen prescription in women 65 years and older with primary breast cancer.
- First-line treatment with epirubicin and vinorelbine in metastatic breast cancer.
- Phase III, multicenter, double-blind, randomized study of letrozole, an aromatase inhibitor, for advanced breast cancer versus megestrol
- False shortening of time to progression in letrozole 2.5-mg dose?
- Letrozole in second-line therapy of advanced breast cancer: more questions than answers.
- Natural modulators of estrogen biosynthesis and function as chemopreventive agents.
- The (-)-enantiomer of gossypol possesses higher anticancer potency than racemic gossypol in human breast cancer.
- Doxorubicin-based adjuvant chemotherapy in elderly breast cancer patients: the M.D. Anderson experience, with long-term follow-up.
- Doxorubicin-based chemotherapy in the elderly.
- Proceedings of the First International Conference on Recent Advances and Future Directions in Endocrine Therapy for Breast Cancer: summary
- Prospects for combining hormonal and nonhormonal growth factor inhibition.
- The role of tamoxifen and aromatase inhibitors/inactivators in postmenopausal patients.
- Are differences in the available aromatase inhibitors and inactivators significant?
- Endocrine manipulation in advanced breast cancer: recent advances with SERM therapies.
- Neoadjuvant endocrine therapy for breast cancer: medical perspectives.
- Current status of adjuvant endocrine therapy for breast cancer.
- Preliminary data from ongoing adjuvant aromatase inhibitor trials.
- Future use of selective estrogen receptor modulators and aromatase inhibitors.
- Who should not receive adjuvant chemotherapy? International databases.
- Who should not receive chemotherapy? Data from American databases and trials.
- Overview of the six available randomized trials of high-dose chemotherapy with blood or marrow transplant in breast cancer.
- Side effects, quality-of-life issues, and trade-offs: the patient perspective.
- Impact of tamoxifen adjuvant therapy on symptoms, functioning, and quality of life.
- Side effects of chemotherapy and combined chemohormonal therapy in women with early-stage breast cancer.
- Patient preferences for adjuvant chemotherapy of early breast cancer: how much benefit is needed?
- Adjuvant therapy for breast cancer: current controversies and future prospects.
- Prognostic and predictive role of proliferation indices in adjuvant therapy of breast cancer.
- Efficacy of systemic adjuvant therapy for breast cancer in African-American and Caucasian women.
- Adjuvant therapy for very young women with breast cancer: need for tailored treatments.
- Factors used to select adjuvant therapy of breast cancer in the United States: an overview of age, race, and socioeconomic status.
- Duration of adjuvant tamoxifen therapy.
- Findings from recent National Surgical Adjuvant Breast and Bowel Project adjuvant studies in stage I breast cancer.
- Progress in systemic chemotherapy of primary breast cancer: an overview.
- Is Her2 of value in identifying patients who particularly benefit from anthracyclines during adjuvant therapy? A qualified yes.
- Is HER-2/neu a predictor of anthracycline utility? No.
- Taxanes in the adjuvant treatment of breast cancer: why not yet?
- Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel
- Real-world performance of HER2 testing--ational Surgical Adjuvant Breast and Bowel Project experience.
- Flare and tumor lysis syndrome with atypical features after letrozole therapy in advanced breast cancer. A case report.
- Sequence- and time-dependent antagonism between raloxifene and methotrexate in human breast cancer cells.
- Functional repression of estrogen receptor a by arsenic trioxide in human breast cancer cells.
- Chemosensitization of T-47D breast carcinoma cells to TRAIL and Fas receptor-induced killing.
- Efficacy of anastrozole in male breast cancer.
- Combination of vinorelbine, epirubicin, and cyclophosphamide as neoadjuvant chemotherapy for locally advanced breast cancer: phase II
- Decision-making in early breast cancer: guidelines and decision tools.
- An EORTC-IDBBC phase I study of gemcitabine and continuous infusion 5-fluorouracil in patients with metastatic breast cancer resistant to
- HER2 overexpressing metastatic breast cancer.
- [Current trends in pharmacotherapy of breast cancer]
- Liposome-based drug delivery in breast cancer treatment.
- Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer.
Table of Contents
1
UI - 11888004
AU - Lohrisch C; Piccart MJ
TI -
Standard medical treatment for early breast cancer.
SO - Eur J Cancer 2001 Oct;37 Suppl 7():S45-58
AD - Institut Jules Bordet, Department of Medicine, Brussels, Belgium.
2
UI - 11923125
AU - Bland KI
TI -
Utilization of sentinel lymph node mapping to determine pathologic
outcomes for patients receiving neoadjuvant chemotherapy for locally
advanced breast cancer.
SO - Ann Surg Oncol 2002 Apr;9(3):217-9
3
UI - 11923128
AU - Newman LA; Buzdar AU; Singletary SE; Kuerer HM; Buchholz T; Ames FC;
TI -
Ross MI; Hunt KK
A prospective trial of preoperative chemotherapy in resectable breast
cancer: predictors of breast-conservation therapy feasibility.
SO - Ann Surg Oncol 2002 Apr;9(3):228-34
AD - Department of Surgical Oncology, The University of Texas M. D. Anderson
Cancer Center, Houston, Texas 77030-4009, USA.
BACKGROUND: The role of preoperative chemotherapy for breast cancer is
evolving. We initiated a prospective trial of sequential preoperative
paclitaxel and doxorubicin-based combination chemotherapy in patients
with stage I (tumor >1 cm), II, or IIIA disease and evaluated its effect
on breast-conservation therapy (BCT) eligibility. METHODS: Pathology
findings for the initial 100 consecutive patients who underwent surgery
were analyzed. RESULTS: The median tumor size at presentation was 2.4
cm, and 39% of patients were deemed eligible for BCT. After
chemotherapy, the median tumor size decreased to 1.0 cm (P <.001), and
59% of patients seemed BCT eligible (BCT conversion rate 34% among
patients initially assessed as BCT ineligible; P <.001). Final pathology
confirmed BCT feasibility in 90% of patients assessed as BCT candidates
before surgery. The pathology from mastectomy specimens revealed BCT
feasibility in 11 (27%) of 41 patients deemed BCT ineligible.
Multivariate analysis revealed lobular histology, multicentricity, and
calcifications, but not age, initial tumor size, or nodal status to
predict final pathology indicating BCT ineligibility. CONCLUSIONS:
Induction chemotherapy improves BCT eligibility for breast cancer
patients. Improved breast imaging methods after chemotherapy are
necessary to improve accuracy in predicting the feasibility of BCT,
especially in patients presenting with diffuse calcifications or
multicentricity.
4
UI - 11923129
AU - Stearns V; Ewing CA; Slack R; Penannen MF; Hayes DF; Tsangaris TN
TI -
Sentinel lymphadenectomy after neoadjuvant chemotherapy for breast
cancer may reliably represent the axilla except for inflammatory breast
cancer.
SO - Ann Surg Oncol 2002 Apr;9(3):235-42
AD - Breast Cancer Program, Department of Oncology, Lombardi Cancer Center,
Georgetown University School of Medicine, Washington, DC, USA.
stearnsv@umich.edu
BACKGROUND: After neoadjuvant chemotherapy, women with locally advanced
breast cancer (LABC) undergo a modified radical mastectomy or lumpectomy
with axillary lymph node dissection (ALND) and radiotherapy. Sentinel
lymphadenectomy (SL) is accepted for axillary evaluation in early breast
cancer. We assessed the feasibility and predictive value of SL after
neoadjuvant chemotherapy. METHODS: Eligible women received neoadjuvant
therapy for LABC and were scheduled to undergo a definitive surgical
procedure. Vital blue dye SL was attempted followed by level I and II
axillary dissection. RESULTS: SL was successful in 29 of 34 patients
(detection rate, 85%). Thirteen patients (45%) had positive nodes, and
eight (28%) had negative nodes on both SL and ALND. In five patients
(17%), the sentinel node was the only positive node identified. Overall,
there was a 90% concordance between SL and ALND. The false-negative rate
and negative predictive value were 14% and 73%, respectively. Among the
subgroup without inflammatory cancer, the detection and concordance
rates were 89% and 96%, respectively. The false-negative rate was 6%,
and the negative predictive value was 88%. CONCLUSIONS: SL after
neoadjuvant chemotherapy may reliably predict axillary staging except in
inflammatory breast cancer. Further studies are required to assess the
utility of SL as the only mode of axillary evaluation in these women.
5
UI - 11923130
AU - Miller AR; Thomason VE; Yeh IT; Alrahwan A; Sharkey FE; Stauffer J; Otto
TI -
PM; McKay C; Kahlenberg MS; Phillips WT; Cruz AB Jr
Analysis of sentinel lymph node mapping with immediate pathologic review
in patients receiving preoperative chemotherapy for breast carcinoma.
SO - Ann Surg Oncol 2002 Apr;9(3):243-7
AD - Division of Surgery, University of Texas Health Science Center at San
Antonio, Texas 78229, USA. millerar@uthscsa.edu
BACKGROUND: Sentinel lymph node mapping (SLNM) and neoadjuvant
chemotherapy are becoming established components of therapy for selected
patients with breast carcinoma. However, neoadjuvant therapy has been
considered a relative contraindication to SLNM. In an effort to learn
whether patients who have received preoperative chemotherapy can undergo
accurate SLNM, we evaluated our experience with this technique. METHODS:
were concurrently performed in 35 patients who received preoperative
chemotherapy. Mapping was performed with (99m)Tc sulfur colloid only in
one patient and Lymphazurin dye only in 15 patients, and the two methods
were combined in the remainder. RESULTS: SLNM successfully identified a
sentinel lymph node in 30 (86%) patients. Metastatic disease was
identified in the sentinel lymph nodes of four patients during surgery.
The intraoperative pathologic diagnosis proved to be correct in 19 (79%)
of 24 patients. The final pathologic diagnosis of the sentinel lymph
node reflected the status of the axillary contents in all patients in
whom it was identified. CONCLUSIONS: These results demonstrate that SLNM
can be consistently performed in patients receiving preoperative
chemotherapy for breast cancer, suggesting the utility of this technique
in this patient population.
6
UI - 11993590
AU - Hooper SB; Hill AD; Kennedy S; Dijkstra B; Kelly LM; McDermott EW;
TI -
O'Higgins N
Tamoxifen as the primary treatment in elderly patients with breast
cancer.
SO - Ir J Med Sci 2002 Jan-Mar;171(1):28-30
AD - Department of Surgery, St Vincent's University Hospital, Dublin,
Ireland.
BACKGROUND: With the increasing incidence of breast cancer in patients
over 70 years, there is interest in the best therapeutic approach. AIMS:
To review the management of breast cancer in elderly women and to
identify the factors involved in the decision to treat patients with
tamoxifen as first line therapy. PATIENTS AND METHODS: Between 1986 and
1999, 302 female patients aged > or = 70 years presented with primary
breast cancer, of whom 219 underwent surgery, 79 received tamoxifen as
first line treatment and four received primary radiotherapy. A
retrospective review was performed on these 79 patients and the outcome
recorded. RESULTS: Of these 79 patients, data was available on 68.
Follow-up ranged from one to 63 months (median 17 months). Co-morbidity
was the principal reason for choosing first line tamoxifen therapy in
61% and patient preference in 11%. Tumour size was less than 5cm in 51%.
In 25% tumour size decreased, in 24% it remained stable and in 27% it
increased in size following tamoxifen therapy. Additional treatment was
prescribed for 33% of patients. CONCLUSION: In the authors' experience,
for those elderly patients suffering considerable co-morbidity or who
refuse surgical intervention, tamoxifen is an acceptable alternative.
7
UI - 11993605
AU - Kennedy MJ
TI -
The limits of tamoxifen.
SO - Ir J Med Sci 2002 Jan-Mar;171(1):8-9
8
UI - 12011135
AU - Zelek L; Cottu P; Tubiana-Hulin M; Vannetzel JM; Chollet P; Misset JL;
TI -
Chouaki N; Marty M; Gamelin E; Culine S; Dieras V; Mackenzie S;
Spielmann M
Phase II study of oxaliplatin and fluorouracil in taxane- and
anthracycline-pretreated breast cancer patients.
SO - J Clin Oncol 2002 May 15;20(10):2551-8
AD - Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif,
France.
PURPOSE: Phase II study evaluating efficacy and safety of combined
oxaliplatin/fluorouracil (5-FU) in taxane-pretreated advanced and
metastatic breast cancer (ABC) patients. PATIENTS AND METHODS:
Sixty-four taxane- and anthracycline-pretreated (within 6 months of
study entry) women were treated with oxaliplatin 130 mg/m(2) (2-hour
intravenous [IV] infusion), day 1, and 5-FU 1,000 mg/m(2)/d (continuous
IV infusion) days 1 to 4, every 3 weeks. RESULTS: Median patient age was
51 years (range, 34 to 71 years), with a median of two involved organs
(range, one to six organs), and metastases in the liver (70%), bone
(47%), and lung (34%). Patients had a median of two prior chemotherapy
regimens (range, one to six regimens), and 78% had previous hormonal
therapy, with clinical taxane and anthracycline resistance in 53% and
34%, respectively. A total of 367 cycles were administered, with a
median of six cycles/patient (range, one to 15 cycles). Sixty patients
were assessable for response (World Health Organization criteria): 17
partial response, 26 stable disease, and 17 disease progression, giving
an overall response rate of 27% (95% confidence interval, 16.3% to
39.1%), and 26% and 36% in taxane- and anthracycline-resistant
populations, respectively, all responders having metastatic liver
disease. Median time to progression was 4.8 months, and median overall
survival was 11.9 months. Four treatment-related serious adverse events
occurred, seven patients withdrew because of treatment-related toxicity.
Hematotoxicity was prevalent but rarely severe, with grade 3-4
neutropenia, leukopenia, and thrombocytopenia in 34%, 19%, and 16% of
patients, respectively, and a single episode of febrile neutropenia. One
third of patients developed grade 2-3 peripheral neuropathy
(oxaliplatin-specific scale), with grade 3 in only 8%. CONCLUSION: This
oxaliplatin/5-FU combination is effective with an excellent safety
profile in anthracycline/taxane-pretreated ABC patients, showing
encouraging activity in patients with anthracycline/taxane-resistance or
visceral disease.
9
UI - 12011136
AU - Love RR; Duc NB; Allred DC; Binh NC; Dinh NV; Kha NN; Thuan TV; Mohsin
TI -
SK; Roanh le D; Khang HX; Tran TL; Quy TT; Thuy NV; The PN; Cau TT; Tung
ND; Huong DT; Quang le M; Hien NN; Thuong L; Shen TZ; Xin Y; Zhang Q;
Havighurst TC; Yang YF; Hillner BE; DeMets DL
Oophorectomy and tamoxifen adjuvant therapy in premenopausal Vietnamese
and Chinese women with operable breast cancer.
SO - J Clin Oncol 2002 May 15;20(10):2559-66
AD - University of Wisconsin Comprehensive Cancer Center, 610 Walnut Street,
Madison, WI 53705-2397, USA. rrlove@facstaff.wisc.edu
PURPOSE: In 1992, the Early Breast Cancer Trialists' Collaborative Group
reported that a meta-analysis of six randomized trials in European and
North American women begun from 1948 to 1972 demonstrated disease-free
and overall survival benefit from adjuvant ovarian ablation.
Approximately 350,000 new cases of breast cancer are diagnosed annually
in premenopausal Asian women who have lower levels of estrogen than
western women. PATIENTS AND METHODS: From 1993 to 1999, we recruited 709
premenopausal women with operable breast cancer (652 from Vietnam, 47
from China) to a randomized clinical trial of adjuvant oophorectomy and
tamoxifen (20 mg orally every day) for 5 years or observation and this
combined hormonal treatment on recurrence. At later dates estrogen- and
progesterone-receptor protein assays by immunohistochemistry were
performed for 470 of the cases (66%). RESULTS: Treatment arms were well
balanced. With a median follow-up of 3.6 years, there have been 84
events and 69 deaths in the adjuvant treatment group and 127 events and
91 deaths in the observation group, with 5-year disease-free survival
rates of 75% and 58% (P =.0003 unadjusted; P =.0075 adjusted), and
overall survival rates of 78% and 70% (P =.041 unadjusted) for the
adjuvant and observation groups, respectively. Only patients with
hormone receptor-positive tumors benefited from the adjuvant treatment.
In Vietnam, for women unselected for hormone receptor status, a
cost-effectiveness analysis suggests that this intervention costs $350
per year of life saved. CONCLUSION: Vietnamese and Chinese women with
hormone receptor-positive operable breast cancer benefit from adjuvant
treatment with surgical oophorectomy and tamoxifen.
10
UI - 11929341
AU - Goss PE; Strasser K
TI -
Tamoxifen resistant and refractory breast cancer: the value of aromatase
inhibitors.
SO - Drugs 2002;62(6):957-66
AD - Breast Cancer Prevention Program, Princess Margaret Hospital, University
Health Network, Toronto, Ontario, Canada. pegoss@interlog.com
Tamoxifen has dominated endocrine treatment of breast cancer for over
two decades. It is useful in metastatic breast cancer, adjuvant therapy,
preoperative treatment, ductal carcinoma-in-situ and chemoprevention.
However, breast cancer may be refractory to tamoxifen or develop
resistance to it with ongoing treatment. This resistance involves
several mechanisms including receptor mutation causing 'estrogen
hypersensitivity' and an increasing agonist effect of tamoxifen.
Megestrol (megestrol acetate), in North America, and aminoglutethimide,
in Europe, have been the traditional second line therapies after
tamoxifen in advanced breast cancer. Aromatase (estrogen synthetase)
inhibitors are a logical alternative to tamoxifen to antagonise the
effects of estrogen on breast cancer. The third-generation non-steroidal
aromatase inhibitors anastrozole, letrozole and vorozole, and the
steroidal inhibitor exemestane, have been studied after tamoxifen versus
either megestrol or aminoglutethimide. They showed enhanced efficacy and
significantly superior toxicity profiles. Compliance with the inhibitors
was also significantly better than with the traditional treatments.
Aromatase inhibitors have most recently been shown to be superior to
tamoxifen as initial therapy and are being extensively tested in the
adjuvant setting after, or instead of, tamoxifen. Pilot studies of
chemoprevention are also being undertaken. The aromatase inhibitors are
an important new addition to the armamentarium of breast cancer therapy.
11
UI - 11929942
AU - Twombly R
TI -
Upstaging tamoxifen? New classes of drugs emerging for breast cancer.
SO - J Natl Cancer Inst 2002 Apr 3;94(7):474-5
12
UI - 12020394
AU - Jones SE
TI -
Antiaromatase agents: evolving role in adjuvant therapy.
SO - Clin Breast Cancer 2002 Apr;3(1):33-42
AD - Charles A. Sammons Cancer Center, Baylor University Medical Center,
Dallas, TX 75246, USA. steve.jones@usoncology.com
The goal of adjuvant hormonal therapy is to prevent breast cancer
recurrence. Standard therapy with tamoxifen has shown great value in the
adjuvant setting; however, its tolerability profile can render it
unsuitable for some patients. The aromatase inactivator, exemestane, and
the 2 aromatase inhibitors, letrozole and anastrozole, have been shown
to be equivalent or superior to tamoxifen with respect to multiple
endpoints in patients with metastatic breast cancer. With tolerability
profiles that are similar to, and in many cases, more acceptable than
that of tamoxifen, and efficacy potentially superior to tamoxifen,
studies using the antiaromatase agents as adjuvant therapy are currently
ongoing. These trials will answer some important questions, such as the
order in which adjuvant hormonal therapies are selected to maximize
efficacy, whether the antiaromatase agents show improved tolerability,
and whether combination therapy is more effective than monotherapy.
13
UI - 12020395
AU - Demetri GD; Gabrilove JL; Blasi MV; Hill RJ Jr; Glaspy J
TI -
Benefits of epoetin alfa in anemic breast cancer patients receiving
chemotherapy.
SO - Clin Breast Cancer 2002 Apr;3(1):45-51
AD - Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
02115, USA. gdemetri@partners.org
Breast cancer patients receiving chemotherapy often exhibit anemia,
which contributes to symptoms such as fatigue, compromising quality of
life (QOL). The present subset analysis assessed the effects of
recombinant human erythropoietin (rHuEPO, epoetin alfa) on anemia and
QOL in approximately 1300 patients with breast cancer, who were derived
from 3 large, community-based clinical trials of epoetin alfa in anemic
chemotherapy patients with various malignancies. Epoetin alfa
effectively and safely corrected anemia and improved QOL scores on the
Linear Analogue Self-Assessment, which measures energy, ability to
perform daily activities, and QOL. Clinical, laboratory, and QOL
improvements were qualitatively and quantitatively similar to those
reported in the larger populations with various tumor types. The
efficacy and safety of epoetin alfa did not vary according to dosing
frequency (1 vs. 3 times weekly). Epoetin alfa is, therefore, effective
and safe in the management of anemia in patients with breast cancer
treated with chemotherapy.
14
UI - 12022477
AU - Pavlov V; Lin PK; Rodilla V
TI -
Biochemical effects and growth inhibition in MCF-7 cells caused by novel
sulphonamido oxa-polyamine derivatives.
SO - Cell Mol Life Sci 2002 Apr;59(4):715-23
AD - Department of Human and Animal Physiology, Faculty of Biology,
University of Sofia St. Kliment Ohridski, Bulgaria.
The novel polyamine derivatives sulphonamido oxa-spermine (oxa-Spm) and
sulphonamido oxa-spermidine (oxa-Spd) exhibited rapid cytotoxic action
towards MCF-7 human breast cancer cells with IC50 values of 4.35 and
6.47 pM, respectively, after 24-h drug exposure. Neither compound is a
substrate of serum amine oxidase. Both oxa-Spm and oxa-Spd caused cell
shrinkage, as determined by phase-contrast microscopy. After incubation
with 10 microM of either compound for 8 h, the cells underwent chromatin
condensation and nuclear fragmentation. However, no clear DNA ladder was
obtained by electrophoresis. The sulphonamido oxa-polyamine derivatives
and especially oxa-Spd enhanced the activity of polyamine oxidase (PAO),
an enzyme capable of oxidising N1-acetylated spermine and spermidine to
spermidine and putrescine, respectively, generating cytotoxic H2O2 and
3-acetamidopropanal as by-products. The intracellular polyamine content
was only marginally reduced in response to drug treatment. In
conclusion, our data show that these novel sulphonamido oxa-polyamine
derivatives possess high cytotoxic activity against MCF-7 cells and
indicate that induction of PAO may mediate their cytotoxicity via
apoptosis.
15
UI - 11900210
AU - Robertson JF
TI -
ICI 182,780 (Fulvestrant)--the first oestrogen receptor
down-regulator--current clinical data.
SO - Br J Cancer 2001 Nov;85 Suppl 2():11-4
AD - Department of Surgery, City Hospital Nottingham, UK.
ICI 182,780 (Fulvestrant) is the first in a new class of novel,
steroidal, 'pure' antioestrogens--the oestrogen receptor (ER)
down-regulators. Its unique mode of action and the absence of partial
agonist activity make it a candidate for the treatment of advanced
breast cancer in both pre- and postmenopausal women. Tamoxifen has been
available for use over the past 25 years. However, its partial agonist
activity has been associated with detrimental effects, particularly on
the endometrium, and may be associated with the development of tamoxifen
resistance. Other antioestrogen agents have previously been unable to
demonstrate clinically relevant activity following the development of
resistance to tamoxifen. In contrast, the unique mechanism of action of
ICI 182,780 results in significant clinical activity in patients failing
on tamoxifen therapy. Indeed, phase III clinical trials have
demonstrated that ICI 182,780 is at least as effective as the aromatase
inhibitor anastrozole in the treatment of postmenopausal patients with
advanced disease who have progressed during threatment with prior
enocrine therapy. As such, ICI 182,780 will provide a valuable addition
to the armamentarium for the treatment of advanced breast cancer.
16
UI - 11900212
AU - Buzdar AU
TI -
Anastrozole (Arimidex)--an aromatase inhibitor for the adjuvant setting?
SO - Br J Cancer 2001 Nov;85 Suppl 2():6-10
AD - Department of Breast Medical Oncology, MD Anderson Cancer Center,
University of Texas, Houston 77030, USA.
Anastrozole (Arimidex) is a third-generation aromatase inhibitor which
has been shown to possess superior efficacy and tolerability over
established endocrine agents in advanced breast cancer. Inhibition of
aromatase prevents the conversion of androgen substrates to oestrogen,
its sole source in postmenopausal women, thereby leading to regression
of hormone-sensitive breast carcinomas. Clinical pharmacology data
indicate that anastrozole is a potent aromatase inhibitor, providing
near-maximal suppression of serum and intratumoural oestrogens to below
detectable levels. Anastrozole may offer greater selectivity compared
with other aromatase inhibitors, being without any intrinsic endocrine
effects and with no apparent effect on the synthesis of adrenal
steroids. It is well tolerated and has a convenient once-daily dosing
regimen, ensuring maximum patient compliance. A major clinical programme
has demonstrated that anastrozole is superior to the standard endocrine
therapy, tamoxifen, for the first-line treatment of postmenopausal women
with hormone-sensitive advanced breast cancer. Its superior efficacy in
advanced disease, together with its improved tolerability and convenient
dosage, make it a suitable agent to be assessed for the treatment of
early breast cancer in postmenopausal women. This was investigated in
the largest single adjuvant breast cancer study ever to be carried out,
the ATAC (Arimidex, tamoxifen, alone or in combination) trial, which has
now completed recruitment, with the first efficacy and safety data
awaited.
17
UI - 11972629
AU - Fagnoni FF; Lozza L; Zibera C; Zambelli A; Ponchio L; Gibelli N;
TI -
Oliviero B; Pavesi L; Gennari R; Vescovini R; Sansoni P; Da Prada G;
Robustelli Della Cuna G
T-cell dynamics after high-dose chemotherapy in adults: elucidation of
the elusive CD8+ subset reveals multiple homeostatic T-cell compartments
with distinct implications for immune competence.
SO - Immunology 2002 May;106(1):27-37
AD - Medical Oncology Division and Surgery Division, Scientific Institute of
Pavia, Fondazione Salvatore Maugeri Clinica del Lavoro e della
Riabilitazione, IRCCS, Pavia, Italy. ffagnoni@fsm.it
Recovery of total T cell numbers after in vivo T-cell depletion in
humans is accompanied by complex perturbation within the CD8+ subset. We
aimed to elucidate the reconstitution of CD8+ T cells by separate
analysis of putative naive CD95- CD28+, memory CD95+ CD28+ and CD28- T
cell compartments after acute maximal depletion by high-dose
chemotherapy (HD-ChT) in women with high-risk breast cancer. We found
that recovery of putative naive CD8+ CD95- CD28+ and CD4+ CD95- CD28+ T
cells, was compatible with a thymus-dependent regenerative pathway since
their recovery was slow and time-dependent, their values were tightly
related to each other, and their reconstitution patterns were inversely
related to age. By analysing non-naive T cells, a striking diversion
between putative memory T cells and CD28- T cells was found. These
latter increased early well beyond normal values, thus playing a pivotal
role in total T-cell homeostasis, and contributed to reduce the CD4 :
CD8 ratio. In contrast, putative memory T cells returned to values not
significantly different from those seen in patients at diagnosis,
indicating that this compartment may recover after HD-ChT. At 3-5 years
after treatment, naive T cells persisted at low levels, with expansion
of CD28- T cells, suggesting that such alterations may extend further.
These findings indicate that CD28- T cells were responsible for 'blind'
T-cell homeostasis, but support the notion that memory and naive T cells
are regulated separately. Given their distinct dynamics, quantitative
evaluation of T-cell pools in patients undergoing chemotherapy should
take into account separate analysis of naive, memory and CD28- T cells.
18
UI - 11986765
AU - Talbot DC; Moiseyenko V; Van Belle S; O'Reilly SM; Alba Conejo E;
TI -
Ackland S; Eisenberg P; Melnychuk D; Pienkowski T; Burger HU; Laws S;
Osterwalder B
Randomised, phase II trial comparing oral capecitabine (Xeloda) with
paclitaxel in patients with metastatic/advanced breast cancer pretreated
with anthracyclines.
SO - Br J Cancer 2002 May 6;86(9):1367-72
AD - Cancer Research UK, Medical Oncology Unit, Churchill Hospital, Oxford
OX3 7LJ, UK.
Capecitabine, an oral fluoropyrimidine carbamate, was designed to
generate 5-fluorouracil preferentially at the tumour site. This
randomised, phase II trial evaluated the efficacy and safety of
capecitabine or paclitaxel in patients with anthracycline-pretreated
metastatic breast cancer. Outpatients with locally advanced and/or
metastatic breast cancer whose disease was unresponsive or resistant to
anthracycline therapy were randomised to 3-week cycles of intermittent
oral capecitabine (1255 mg m(-2) twice daily, days 1-14, (22 patients))
or a reference arm of i.v. paclitaxel (175 mg m(-2), (20 patients)). Two
additional patients were initially randomised to continuous capecitabine
666 mg m(-2) twice daily, but this arm was closed following selection of
the intermittent schedule for further development. Overall response rate
was 36% (95% CI 17-59%) with capecitabine (including three complete
responses) and 26% (95% CI 9-51%) with paclitaxel (no complete
responses). Median time to disease progression was similar in the two
treatment groups (3.0 months with capecitabine, 3.1 months with
paclitaxel), as was overall survival (7.6 and 9.4 months, respectively).
Paclitaxel was associated with more alopecia, peripheral neuropathy,
myalgia and neutropenia, whereas typical capecitabine-related adverse
events were diarrhoea, vomiting and hand-foot syndrome. Twenty-three per
cent of capecitabine-treated patients and 16% of paclitaxel-treated
patients achieved a > or =10% improvement in Karnofsky Performance
Status. Oral capecitabine is active in anthracycline-pretreated
advanced/metastatic breast cancer and has a favourable safety profile.
Furthermore, capecitabine provides a convenient, patient-orientated
therapy. Copyright 2002 Cancer Research UK
19
UI - 11994976
AU - Falanga A; Toma S; Marchetti M; Palumbo R; Raffo P; Consonni R; Marziali
TI -
S; Dastoli G; Barbui T
Effect of all-trans-retinoic acid on the hypercoagulable state of
patients with breast cancer.
SO - Am J Hematol 2002 May;70(1):9-15
AD - Department of Hematology, Ospedali Riuniti, Largo Barozzi, 14128
Bergamo, Italy. annafalanga@yahoo.com
To evaluate whether all-trans-retinoic acid (ATRA) is able to modulate
the hemostatic system in patients with solid tumors, we studied patients
with locally advanced breast cancer who were enrolled in a Phase Ib
study of ATRA +/- Tamoxifen (Tam). In this study, two groups of 15
patients/each were treated for 21 days before operation with ATRA at
three doses (15, 45, or 75 mg/m(2)/day on alternate days) given alone
(group 1) or in combination with Tam (group 2). One additional group
received Tam alone. Plasma samples were evaluated for hypercoagulation
markers (FVIIa, F1+2, TAT, D-dimer), fibrinolysis proteins (t-PA,
PAI-1), and coagulation inhibitors (protein C, AT). At baseline, cancer
patients had FVIIa, F1+2, TAT, and PAI-1 significantly greater than
control subjects. During treatment, in the patients given ATRA alone,
hypercoagulation markers appeared unmodified. Instead, subjects given
Tam alone had a significant elevation of FVIIa, F1+2, and TAT versus
baseline. However, in the ATRA + Tam groups, hypercoagulation markers
were decreased compared with Tam alone. These results suggest that in
selected conditions, pre-operative ATRA may modulate the hypercoagulable
state of breast cancer patients. Copyright 2002 Wiley-Liss, Inc.
20
UI - 12040676
AU - Ishida T; Kusaba T; Hayakawa H
TI -
[Incidence of emesis in outpatients on chemotherapy for breast cancer
and the clinical efficacy of ondansetron hydrochloride tablets]
SO - Gan To Kagaku Ryoho 2002 May;29(5):723-8
AD - Dept. of Surgery, Takasaki National Hospital.
The incidence of nausea and vomiting was investigated for a maximum of 7
days in 32 breast cancer patients receiving CAF (cyclophosphamide,
adriamycin, 5-fluorouracil) and CMF (cyclophosphamide, methotrexate,
5-fluorouracil) therapies. For those patients who experienced nausea and
vomiting, 4 mg/day of ondansetron hydrochloride (OND) in tablet form was
given in the next course of the chemotherapy, and the anti-emetic effect
of the drug was examined. During the observation period, nausea was seen
in 17.2-50.0% of the patients and vomiting in 3.1-15.6%. The number of
patients who had nausea and vomiting was 22. The anti-emetic effect was
examined in 18 out of 22 cases with nausea and vomiting. An anti-emetic
effect based on the judgement criterion (efficacy rate) was seen in
94.4% or more of patients for all the days of observation. A marked
effect was seen in higher proportion of patients. In conclusion, nausea
and vomiting occurred in 17.2-50.0% of the breast cancer patients on
chemotherapy (CAF and CMF therapies). To improve the QOL of those
patients, anti-emetic treatment using OND tablets as necessary is
considered to be effective.
21
UI - 12040677
AU - Abe R; Tominaga T; Nomizu T; Nomura Y; Takashima S; Koyama H; Sano M;
TI -
Tohge T; Ueo H; Ikeda S; Ohashi Y; CGS20267 Study Group
[CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study
for postmenopausal women with advanced or recurrent breast cancer (no.
1)--investigation of recommended clinical dose CGS20267 Study Group]
SO - Gan To Kagaku Ryoho 2002 May;29(5):729-40
AD - Dept. of Surgery II, Fukushima Medical College.
To determine the recommended clinical dose of CGS20267 (Letrozole), we
conducted a randomized comparative study as a late phase II study (first
part) in postmenopausal women with advanced or recurrent breast cancer.
Forty-one patients were randomly assigned to receive 0.5 mg or 1.0 mg
once daily. There were no statistically significant differences in
background between the two groups. Although there was no significant
difference in the objective response rates between the two groups, the
rate was higher at 1.0 mg (44.4%) than at 0.5 mg (38.1%). We also
combined these data with the results of an early phase II study. The
objective response rates (CR + PR) were 31.4% at 0.5 mg and 42.2% at 1.0
mg, and response rates consisting of CR, PR, and NC for longer than 6
months were significantly higher at a dose of 1.0 mg (68.9%) than 0.5 mg
(41.2%). Side effects included drug-related adverse events in 36.8% at
0.5 mg and in 31.6% at 1.0 mg. All of the events were grade 2 or lower,
indicating a favorable tolerability of CGS20267. These results
demonstrated that CGS20267 1.0 mg once daily is more effective than 0.5
mg, and has comparable safety, in the treatment of postmenopausal women
with advanced or recurrent breast cancer. We conclude the recommended
clinical dose of CGS20267 should be 1.0 mg once daily.
22
UI - 12040678
AU - Kimijima I; Tominaga T; Nomizu T; Nomura Y; Takashima S; Koyama H; Sano
TI -
M; Tohge T; Ueo H; Ikeda S; Ohashi Y; CGS20267 Study Group
[CGS20267 (Letrozole), a new aromatase inhibitor: late phase II study in
postmenopausal women with advanced or recurrent breast cancer (no.
2)--evaluation of efficacy and safety at the recommended clinical dose
CGS20267 Study Group]
SO - Gan To Kagaku Ryoho 2002 May;29(5):741-9
AD - Dept. of Surgery II, Fukushima Medical College.
In the first part of this late phase II study, we determined the
recommended clinical dose of CGS20267 to be 1.0 mg once daily for the
treatment of postmenopausal women with advanced or recurrent breast
cancer. To further evaluate the efficacy and safety of CGS20267 at the
derived or recommended clinical dose, 30 more patients were enrolled in
the second part of the study, and were added to the patients treated at
1.0 mg in the first part. As a result of putting the first and second
parts together, the objective response rate at 1.0 mg was found to be
38.3%, which was almost equal to that of the early phase II study
(40.7%). Drug-related adverse events occurred in 35.4% of the patients
at 1.0 mg, and all of the events were of grade 2 or lower. These results
demonstrated that CGS20267 1.0 mg once daily is effective and well
tolerated in the treatment of postmenopausal women with advanced or
recurrent breast cancer.
23
UI - 12040686
AU - Kusama M; Kaise H; Nakayama S; Ota D; Aoki T; Koyanagi Y; Misaka T;
TI -
Matunaga T
[A case of breast cancer with multiple bone metastases that responded
remarkably to doxifluridine (5'-DFUR), cyclophosphamide (CPA),
medroxyprogesterone acetate (MPA) and pamidronate disodium therapy]
SO - Gan To Kagaku Ryoho 2002 May;29(5):785-9
AD - 3rd Dept. of Surgery, Tokyo Medical University.
A 49-year-old female underwent bilateral breast preserving surgery for
heterochronic breast cancers. She later developed a sternal metastasis
and was recommended for intravenous chemotherapy. However, she refused
such an intensive therapy and opted for immunotherapy. Afterward, she
came to our hospital because of spinal metastases with back pain. She
was treated with oral administration of 5'-DFUR and MPA 1,200 mg/day for
3 weeks, respectively, CPA 100 mg/day for 2 weeks, and pamidronate
disodium 30 mg intravenously every 4 weeks. This combined chemotherapy
relieved her pain after one course. After 5 courses, tumor markers were
reduced to the normal range. After 14 courses, bone X-P revealed that
the osteolytic bone showed sclerotic changes and bone scintigraphy
showed a complete remission (CR). The adverse effects were not
remarkable. This regimen is possible on an outpatient basis, and it may
play an important role from the standpoint of treatment effectiveness
and the quality of life of the patient.
24
UI - 12045065
AU - Esmaeli B; Hortobagyi GN; Esteva FJ; Booser D; Ahmadi MA; Rivera E;
TI -
Arbuckle R; Delpassand E; Guerra L; Valero V
Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel
in patients with metastatic breast cancer.
SO - Ophthalmology 2002 Jun;109(6):1188-91
AD - Ophthalmology Section, Department of Plastic Surgery, The University of
Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
PURPOSE: To compare the frequency of canalicular stenosis as a side
effect of weekly versus every-3-weeks docetaxel in patients with
metastatic breast cancer. DESIGN: Retrospective nonrandomized
comparative trial. PATIENTS AND METHODS: Eighteen patients enrolled in a
phase II study of weekly docetaxel plus trastuzumab and 18 patients
enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin
were evaluated. Each patient underwent a comprehensive ophthalmologic
examination, probing and irrigation of the nasolacrimal duct, and, in
some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If
epiphora (excessive tearing) was reported by the patient, its time of
onset was documented. In patients with epiphora, presence or absence of
canalicular stenosis was evaluated on the basis of the findings on
probing and irrigation. The duration of treatment with docetaxel, the
dose frequency, and the cumulative dose of docetaxel were recorded in
each case. RESULTS: Fourteen patients (77%) receiving weekly docetaxel
plus trastuzumab had epiphora. Nine of these patients had significant
anatomic narrowing of the canaliculi. Bicanalicular silicone intubation
or dacryocystorhinostomy was recommended in all nine patients. Eight
patients underwent surgery and experienced complete or near complete
resolution of epiphora. Although two patients (11%) receiving
every-3-weeks docetaxel plus doxorubicin reported transient symptoms of
epiphora, neither patient was found to have narrowing of the canaliculi,
and the epiphora was not severe enough to justify surgical intervention.
The mean duration of docetaxel therapy for the patients in this study
was 19 weeks. The mean cumulative dose of docetaxel was higher in
patients with canalicular stenosis than in patients without this side
effect. CONCLUSIONS: Canalicular stenosis was more common in patients
receiving weekly docetaxel than in those receiving every-3-weeks
docetaxel for metastatic breast cancer. Bicanalicular silicone
intubation early in the course of weekly docetaxel therapy should be
considered, because this intervention can prevent complete closure of
the canaliculi. Once complete or near complete stenosis of the
canaliculi occurs, placement of a permanent Pyrex glass tube may become
necessary to overcome the blockage of tear outflow.
25
UI - 11905711
AU - Smith IE; Lipton L
TI -
Preoperative/neoadjuvant medical therapy for early breast cancer.
SO - Lancet Oncol 2001 Sep;2(9):561-70
AD - Breast Unit, Royal Marsden NHS Trust, London, UK.
ian.smith@rmh.nthames.nhs.uk
Preoperative (neoadjuvant) medical therapy has emerged over the past
decade as a new approach for the treatment of early breast cancer.
Results show it has high activity, but survival is no better than with
conventional adjuvant treatment. The need for mastectomy is reduced but
not abolished; in some studies this effect is associated with a small
increase in risk of local recurrence, but without any detriment to
survival. Predictive factors for improved outcome include clinical
response, and especially pathological complete remissions. However,
persisting pathological axillary node involvement is associated with
poor outcome. Biological changes in apoptosis or proliferation pathways
may prove to be more sensitive surrogate markers than clinical or
pathological responses for assessing treatment outcome. The main
long-term aim of preoperative medical treatment must be to establish
such surrogate predictive markers. This would lead to individualised
treatment for each patient, and would allow much more rapid assessment
of new drugs than is currently possible with adjuvant therapy trials.
26
UI - 11905722
AU - Adlard JW; Dodwell DJ
TI -
Optimum anthracycline-based chemotherapy for early breast cancer.
SO - Lancet Oncol 2001 Aug;2(8):469-74
AD - Yorkshire Centre for Clinical Oncology, Cookridge Hospital, Leeds, UK.
jwa@doctors.org.uk
Adjuvant chemotherapy improves the overall survival of women treated
after surgery for early breast cancer. Several trials have suggested
that anthracycline-containing regimens are more effective than those
that do not contain anthracyclines. A modest overall benefit has also
been confirmed by the Early Breast Cancer Trialists' Collaborative Group
overview. Newer agents, such as the taxanes, are now being tested in the
adjuvant setting in randomised trials. The control group of such studies
should receive the optimum standard treatment. There are several
anthracycline-based regimens in common use, varying in terms of the type
of anthracycline used, the dose, and drug scheduling. We review the
available evidence and consider whether the optimum
anthracycline-containing chemotherapy schedule has now been identified.
27
UI - 12001113
AU - Vincent-Salomon A; Jouve M; Genin P; Freneaux P; Sigal-Zafrani B; Caly
TI -
M; Beuzeboc P; Pouillart P; Sastre-Garau X
HER2 status in patients with breast carcinoma is not modified
selectively by preoperative chemotherapy and is stable during the
metastatic process.
SO - Cancer 2002 Apr 15;94(8):2169-73
AD - Department of Pathology, Institut Curie, Paris, France.
BACKGROUND: The objective of this study was to determine whether HER2
expression levels in breast carcinomas were modified by chemotherapy or
during the metastatic process. METHODS: HER2 expression was analyzed on
sequential tissue specimens taken from the primary tumor before patients
received preoperative chemotherapy (CT) and from post-CT residual breast
tumor or at a metastatic site. The first group of patients included 59
women who presented with T2-T4,N1-N2 breast carcinoma and were treated
by preoperative anthracycline-based CT and then underwent surgery. The
second group included 44 patients with metastatic breast carcinoma
localized to the lung (27 patients) or to the liver (17 patients). HER2
status was determined by immunohistochemistry using an
anti-p185(HER/neu) monoclonal antibody and was classified as
overexpressed or not overexpressed. RESULTS: Among the patients who
received preoperative CT, HER2 overexpression was observed in 15 of 59
patients (25%). A complete pathologic response was observed in 2 of
these 15 patients. HER2 still was overexpressed in 11 of 13 remaining
residual tumors and was no longer detectable in 2 tumors. In addition,
the 29 tumors with no HER2 overexpression before CT remained negative
after treatment. In patients with metastatic breast carcinoma, HER2 was
overexpressed in 11 of 44 primary tumors (25%). In 9 of these 11 tumors,
HER2 overexpression was maintained in the metastases (9 pulmonary
metastases and 4 hepatic metastases). In two patients who had low levels
of HER2 overexpression in their primary tumors, no
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