Prolonged time to progression with fulvestrant for metastatic breast cancer

Abstract

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.

Biological effects of fulvestrant on estrogen receptor positive human breast cancer: short, medium and long‐term effects based on sequential biopsies

“…Although patient number precluded meaningful analysis of pER or Bcl‐2, PD patients were commonly PR negative at baseline suggesting classical estrogen/ER signaling is needed to achieve CB with fulvestrant. However, these PR findings remain clinically controversial . Moreover, tissue inhibitor of metalloproteinases 1 (TIMP‐1) overexpression has been noted to promote PR loss and fulvestrant resistance in vitro potentially via modifying nonclassical ER activity .…”

“…However, these PR findings remain clinically controversial. 29,30 Moreover, tissue inhibitor of metalloproteinases 1 (TIMP-1) overexpression has been noted to promote PR loss and fulvestrant resistance in vitro potentially via modifying nonclassical ER activity. 31 Fulvestrant promoted a timedependent fall in PR and Bcl-2 (and modest pER decline in about 50% patients) in our series by 6 months.…”

Avaliação >i<in vitro>/i< da associação farmacológica entre Genisteína e quimioterápicos no tratamento de câncer de mama

“…Em relação ao REβ, este fármaco estabiliza tal receptor de forma a contribuir para seus efeitos antiproliferativos(65). Ainda, estudos mostram que o Fulvestranto também é capaz de infrarregular tanto os RPs quanto o fator de proliferação Ki-67 em tumores de mama(65,66), além de também inibir a aromatase(67). Devido a tais propriedades, tumores resistentes ao Tamoxifeno e aos inibidores da aromatase, em geral, continuam sensíveis ao Fulvestranto(59,64), sendo este fármaco utilizado como segunda ou terceira linha de tratamento para carcinoma de mama no Brasil (45) e cuja eficácia é notável em tumores metastáticos(66).…”

“…Ainda, estudos mostram que o Fulvestranto também é capaz de infrarregular tanto os RPs quanto o fator de proliferação Ki-67 em tumores de mama(65,66), além de também inibir a aromatase(67). Devido a tais propriedades, tumores resistentes ao Tamoxifeno e aos inibidores da aromatase, em geral, continuam sensíveis ao Fulvestranto(59,64), sendo este fármaco utilizado como segunda ou terceira linha de tratamento para carcinoma de mama no Brasil (45) e cuja eficácia é notável em tumores metastáticos(66). Logo, este SERD é aplicado na dose mensal de 250-500mg via intramuscular (45) e o tempo de tratamento médio para a transição deste fármaco para o próximo (SERM ou inibidor da aromatase) é de 6 meses(64).…”