Ann Oncol. 2009 Oct 29. [Epub ahead of print]
Activity of fulvestrant in HER2-overexpressing advanced breast cancer.
FULL TEXT
Robertson JF, Steger GG, Neven P, Barni S, Gieseking F, Nolè F, Pritchard KI, O'Malley FP, Simon SD, Kaufman B, Petruzelka L.
Professorial Unit of Surgery, Division of Breast Surgery, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
BACKGROUND: Human epidermal growth factor receptor 2 (HER2) overexpression increases the aggressiveness of breast cancer cells resulting in poorer prognosis.
Patients with HER2-positive disease are less responsive to endocrine therapies. Trastuzumab monotherapy results in objective responses in only approximately 15% of patients.
Fulvestrant retains activity in cells overexpressing HER2 that are resistant to other endocrine treatments. This retrospective study evaluated response to fulvestrant treatment among HER2-positive patients with advanced breast cancer (ABC). PATIENTS AND METHODS: Clinical experience data from 10 treatment centres were pooled. Postmenopausal patients with predominantly hormone receptor-positive and HER2-positive disease were included. Clinical benefit (CB) was defined as the proportion of patients achieving a response to treatment (partial or complete) or stable disease lasting >/=6 months. RESULTS: Data for 102 patients were analysed.
Fulvestrant resulted in an overall CB rate of 42% (43/101) in HER2-positive patients and 40% (25/63) in patients with visceral disease. Median duration of treatment was 14.5 months (range 6-44 months).
Fulvestrant showed activity up to the fourth line of endocrine therapy and up to the seventh line of overall therapy. CONCLUSIONS: Results indicate that fulvestrant
may be a suitable treatment option in extensively pre-treated patients with HER2-positive, hormone receptor-positive ABC. Further exploration of its use in this patient population is warranted.
PMID: 19875750
(NOTE: The above study used the original low dose (250mg/monthly dose..might do better at newer 500mg recommendation)
Breast Cancer Res Treat. 2009 Nov;118(2):377-83. Epub 2009 Jun 24.
Predicting benefit from fulvestrant in pretreated metastatic breast cancer patients.
Freedman O,
Amir E,
Dranitsaris G,
Napolskikh J,
Kumar R,
Fralick M,
Chia S,
Petrella T,
Dent S,
Tonkin K,
Ahmad I,
Rayson D,
Clemons M.
Division of Medical Oncology, Princess Margaret Hospital, Suite 5-205, 610 University Avenue, Toronto, ON, M5G 2M9, Canada.
Fulvestrant use in pretreated metastatic breast cancer patients is associated with variable response rates. This study aimed to characterize these responses and to develop a prediction model to identify those patients who could potentially derive the most clinical benefit.
A nationwide review of patients enrolled in a Canadian compassionate use program from 1999 to 2006 was performed. Prior therapy with tamoxifen, steroidal, and nonsteroidal aromatase inhibitors was mandatory. The dependent variable in the analysis was the proportion of patients requiring chemotherapy at 3 months following the start of fulvestrant. General Linear Mixed modeling was used to identify factors significantly associated with this dependent variable and to subsequently develop the prediction model. Three hundred and five women received at least one dose of fulvestrant; 207 went on to receive chemotherapy (68%). Median duration of fulvestrant treatment was 4.1 months (range 0.8-63.1).
Factors predictive of being chemotherapy free at 3 months included older age, no prior adjuvant hormonal therapy, and the absence of lung or brain metastases at the start of therapy. A receiver operating characteristic (ROC) curve analysis had an area under the curve of 0.70 (95% CI 0.60-0.80). This model was able to identify risk information that could be helpful in assessing which patients would most likely benefit from fulvestrant as an intervention with the objective being a delay in chemotherapy.
PMID: 19551499 [PubMed - indexed for MEDLINE]
Text:
http://www.cinj.org/documents/PRAACR...hfield0309.pdf
Contact: Michele Fisher
Media Relations Specialist 732/235-9872
fisherm2@umdnj.edu
Researchers Find Way to Maximize Treatment for Estrogen Receptive Positive Breast Cancer
Study from The Cancer Institute of New Jersey Presented at 100th Annual AACR Meeting
New Brunswick, N.J., April 20, 2009 – Researchers from The Cancer Institute of New Jersey (CINJ) are converging on Denver for the 100th Annual Meeting of the American Association for Cancer Research (AACR) to share their findings on a combined treatment targeting breast cancer that is stimulated by the hormone estrogen (estrogen receptive positive). They are joining other top investigators from around the globe for the event, which is highlighting interdisciplinary approaches to cancer research. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson Medical School.
Among the abstracts being presented is one focusing on how the FDA-approved therapy fulvestrant can influence the effects of chemotherapy drugs on breast cancer cells. Fulvestrant is commonly used in postmenopausal women to treat estrogen receptive positive breast cancer that has spread to other parts of the body.
Breast cancers that respond to female hormones, such as estrogen, generate specific proteins that help tumor cells survive and grow. One such protein, HDM2, is known to be present in higher levels in many cancers including breast. These higher protein levels are strongly correlated with the presence of the estrogen receptor on breast cancer cells, which can affect how well chemotherapy works. Targeting the receptor is a common treatment for breast cancer.
Lead author Adriana V. Jager, PhD, a postdoctoral fellow at CINJ, and her colleagues focused on adding fulvestrant to the traditional chemotherapy agents doxorubicin, etoposide and paclitaxel, as fulvestrant is known to degrade the estrogen receptor and result in less stimulation of tumor cell growth. They found that in two estrogen receptor positive breast cancer cell lines, fulvestrant decreased HDM2 levels and enhanced the sensitivity of these cells to chemotherapy. This enhancement was better than either fulvestrant or chemotherapy alone.
According to the American Cancer Society, 183,000 cases of breast cancer were diagnosed nationwide last year, with 6,300 new cases in New Jersey alone. With such statistics, the team is hopeful that this laboratory-based research can be expanded to a clinical trial with patients in order to further explore improved outcomes.
The author team also includes William N. Hait, MD, PhD, Johnson and Johnson/Centocor; Deborah Toppmeyer, MD, CINJ; Bruce G. Haffty, MD, CINJ; Kim Hirshfield, MD, PhD, CINJ; and Jin-Ming Yang, PhD, Penn State.
The work represented by CINJ members is among the 6,000 abstracts being presented at the gathering, which is featuring more than 17,000 researchers, healthcare professionals, and patient advocates. The goal of the annual AACR event is to provide a forum in which the latest in cutting-edge laboratory, clinical and translational research can be shared.
About The Cancer Institute of New Jersey
The Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center, and is dedicated to improving the prevention, detection, treatment and care of patients with cancer. CINJ’s physician-scientists engage in translational research, transforming their laboratory discoveries into clinical practice, quite literally bringing research to life. The Cancer Institute of New Jersey is a center of excellence of UMDNJ-Robert Wood Johnson Medical School. To support CINJ, please call the Cancer Institute of New Jersey Foundation at 1-888-333-CINJ.
The Cancer Institute of New Jersey Network is comprised of hospitals throughout the state and provides a mechanism to rapidly disseminate important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. Major Clinical Research Affiliate Hospitals: Carol G. Simon Cancer Center at Morristown Memorial Hospital, Carol G. Simon Cancer Center at Overlook Hospital, Jersey Shore University Medical Center. Affiliate Hospitals: Bayshore Community Hospital, CentraState Healthcare System, Cooper University Hospital*, JFK Medical Center, Raritan Bay Medical Center, Robert Wood Johnson University Hospital at Hamilton (CINJ at Hamilton), Saint Peter’s University Hospital, Somerset Medical Center, Southern Ocean County Hospital, The University Hospital/UMDNJ-New Jersey Medical School*, and University Medical Center at Princeton. *Academic Affiliate
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Cancer Res. 2007 Jun 1;67(11):5337-44.
Estrogen receptor alpha mediates breast cancer cell resistance to paclitaxel through inhibition of apoptotic cell death.
Sui M,
Huang Y,
Park BH,
Davidson NE,
Fan W.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Estrogen receptors (ER) are expressed in approximately 65% of human breast cancer. Cumulative data from clinical trials and retrospective analyses suggest that some chemotherapeutic agents may be less effective in patients with ER-positive (ER+) tumors than those with ER-negative (ER-) tumors. Paclitaxel is an active agent used in breast cancer chemotherapy. To investigate the possible influence of ER on the therapeutic efficacy of paclitaxel and its underlying mechanism, we established several isogenic ER+ cell lines by stable transfection of ERalpha expression vectors into ER- breast cancer BCap37 cells. We showed that 17-beta estradiol significantly reduces the overall cytotoxicity of paclitaxel in BCap37-expressing ERalpha but has no influence on the ER- parental cells. Further analyses indicate that expression of ERalpha in BCap37 cells mainly interferes with paclitaxel-induced apoptotic cell death, without affecting paclitaxel-induced microtubule bundling and mitotic arrest. Moreover,
we found that the addition of ICI 182,780 (Fulvestrant), a selective ER down-regulator, could completely reverse the resistance of ER+ BCap37 cells to paclitaxel. These findings showed that ERalpha-mediated breast tumor cell resistance to paclitaxel was through selective inhibition of paclitaxel-induced tumor cell apoptosis. Additionally, the combination of ICI 182,780
also sensitizes MCF-7 and T47D cell lines to the treatment of paclitaxel, which further confirmed the correlation between ERalpha and drug resistance in ER+ tumor cells.
The results obtained from this study provide useful information for understanding ER-mediated resistance to paclitaxel and possibly other antineoplastic agents.
PMID: 17545614 [PubMed - indexed for MEDLINE]
Video clip from makers of Faslodex on hormonal aspects of BC:
http://www.hormonalaspectsofbc.com/p...211/index.html
Of note is that host says it can take 3 months before effectiveness is shown in hormonal therapy. Tumor can initially enlarge and Markers can rise even when eventually effective.
Med Oncol. 2010 Mar 20. [Epub ahead of print]
Prolonged time to progression with fulvestrant for metastatic breast cancer.
Mello CA,
Chinen LT,
da Silva SC,
do Nascimento Matias C,
Benevides CF,
Gimenes DL,
Fanelli MF.
Fundação Antônio Prudente, Hospital do Câncer A. C. Camargo, Rua Prof Antônio Prudente, 211, Liberdade, São Paulo, SP, 01509-900, Brazil,
celso.mello@hcancer.org.br.
Although the incidence of breast cancer has been declining in recent years, the disease is still one of the leading causes of cancer deaths in women. Recently, breast cancer has been treated with innovative approaches that use hormone-sensitive therapies. This is because in at least one-third of breast cancers, estrogens mediated via the estrogen receptor pathway act as endocrine growth factors.
Fulvestrant has been studied as both first- and second-line therapy for locally advanced and metastatic breast cancer, but few studies have shown its effect as third-line therapy alone. To observe the disease time to progression (TTP) obtained with fulvestrant when used on metastatic breast cancer as first-, second-, and also third-line therapy. We also aimed to correlate the TTP obtained with fulvestrant with hormone receptor, HER2 expression, and metastatic site. This was a cohort study that retrospectively examined medical records of 73 postmenopausal women with
advanced breast cancer who were treated with fulvestrant (250 mg/month i.m. injection) and followed at the Department of Medical Oncology at Hospital do Cancer A. C. Camargo in São Paulo, Brazil from August 2003 to December 2006.
The median TTP with fulvestrant was about 11 months. When used as the first-line therapy, TTP was about 13 months; when used as second-line, TTP was about 6 months; and when used as third-line, it was about 12 months. No statistically significant difference was observed regarding the therapy line. In patients with positive ER tumors, TTP was 11 months. No significant difference in TTP was observed in negative ER tumors (TTP = 10 months).
In patients with positive PgR tumors, TTP was 13 months and for negative PgR, TTP was 6 months (P = 0.008). According to the HER2 status, the TTP was 5 months for HER2+ and 10 months for HER2-. Our findings indicate that fulvestrant is an effective alternative for treatment of metastatic breast cancer.
PMID: 20306159 [PubMed - as supplied by publisher]
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