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Racial and ethnic basis to breast tumours
Newsdesk High incidence of brain metastases with trastuzumab treatment
Oncology Vol 5 September 2004
metastases; these figures might simply mean that the drug is improving patient survival to the point at which brain disease develops and becomes clinically noticeable. Furthermore, HER2-positive breast-cancer metastases might have a predilection for the brain. Unfortunately, however, because trastuzumab does not cross the blood–brain barrier, it is unlikely to prevent the growth of these secondary cerebral tumours. “There’s no apparent reason why trastuzumab should be the cause of brain metastases”, remarked Felix Bonilla, Head Oncologist at the Puerta de Hierro Hospital, Madrid, Spain. “But no-one has compared the incidence of this problem in patients
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
© Robert Harding Picture Library
UK researchers have reported more evidence that associates trastuzumab treatment for HER2 positive breast cancer with a greater incidence of brain metastases (Br J Cancer 2004; 91: 639–43). The reasons, however, could simply be the drug’s efficiency: the improved survival achieved with trastuzumab might be giving brain metastases long enough to develop and become clinically evident. Trastuzumab, a recombinant humanised monoclonal antibody that attaches to over-expressed HER2 receptors in HER2-positive breast cancer, is well known to improve survival, especially combined with chemotherapy. However, women given the drug have a tendency to develop brain metastases. Study leader Andrew Wardley (Christie Hospital NHS Trust, Manchester, UK) adds that their “much larger study would seem to confirm the association, although its exact nature remains unclear”. Wardley and colleagues assessed the medical records of 93 patients with HER2-positive breast cancer who were given trastuzumab to determine how many developed brain metastases after treatment had begun, and to see whether there were any clinical or pathological conditions that might be associated with the complication. As expected, trastuzumab was effective, with 57% of patients showing stable disease or a better response compared with those who did not receive the drug. After 1 year of treatment, however, 26·1% of patients had developed brain metastases. “We found that patients with visceral disease at the beginning of trastuzumab therapy were significantly more likely to develop brain metastases. We also saw some evidence that oestrogen-receptor status might be involved: 35% of the patients with oestrogen-receptornegative tumours developed brain metastases, compared with only 12% of those who were oestrogen-receptor positive”, says Wardley. However, no-one is claiming that trastuzumab is the cause of these
Living longer: nature of trastuzumab unclear.
treated with trastuzumab or other therapy combinations. That might help confirm whether prolonged survival is behind this association.” Adrian Burton
Racial and ethnic basis to breast tumours Black women diagnosed with breast carcinoma are more likely than their white counterparts to develop breast tumours with aggressive features, including alterations in the tumour suppressor gene P53, according to the results of a recent study. To investigate racial and ethnic differences in selected breast-tumour characteristics, Beth Jones, Yale University School of Medicine (New Haven, CT, USA), and colleagues retrieved and analysed the archived tumour-tissue samples of 145 black women and 177 white women who were diagnosed with breast cancer between 1987 and 1989 (Cancer, published online Aug 9, 2004; DOI: 10.1002/ cncr.20500). “In addition to confirming previous findings with regard to tumour stage, histological and nuclear grade, and hormone-receptor status, we also gleaned important new information about the frequency of molecular alterations in P53, HER2/NEU, and C-MET in black and white women with breast cancer”, Jones says. The researchers found that the frequency of alterations in P53 was four times higher in black women than in white women, even after adjustment
http://oncology.thelancet.com
for other tumour characteristics, disease stage, socioeconomic status, obesity, and selected lifestyle factors. Such alterations, which are reported to occur early in carcinogenesis and are associated with poor prognosis, might be responses to endogenous or environmental exposures that can vary between racial or ethnic groups, Jones comments. No significant racial or ethnic differences were seen in the overexpression of the oncogene HER2/ NEU or the proto-oncogene C-MET. Lisa Newman, University of Michigan Comprehensive Cancer Center (Ann Arbor, MI, USA), states that the findings underscore the importance of assessing variation in primary tumour biology in studies of disparities in cancer outcome. “The aetiology for survival disadvantages observed among black cancer patients is likely to be multifactorial and includes issues related to health-care access and delivery, as well as to cancer genetics”, she says. “For the hormonally-driven cancers, such as breast and prostate, the contribution of factors associated with primary tumour biology may be relatively stronger than previously appreciated.” Kathleen Wildasin
523
Oncology Vol 5 September 2004
metastases; these figures might simply mean that the drug is improving patient survival to the point at which brain disease develops and becomes clinically noticeable. Furthermore, HER2-positive breast-cancer metastases might have a predilection for the brain. Unfortunately, however, because trastuzumab does not cross the blood–brain barrier, it is unlikely to prevent the growth of these secondary cerebral tumours. “There’s no apparent reason why trastuzumab should be the cause of brain metastases”, remarked Felix Bonilla, Head Oncologist at the Puerta de Hierro Hospital, Madrid, Spain. “But no-one has compared the incidence of this problem in patients
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
© Robert Harding Picture Library
UK researchers have reported more evidence that associates trastuzumab treatment for HER2 positive breast cancer with a greater incidence of brain metastases (Br J Cancer 2004; 91: 639–43). The reasons, however, could simply be the drug’s efficiency: the improved survival achieved with trastuzumab might be giving brain metastases long enough to develop and become clinically evident. Trastuzumab, a recombinant humanised monoclonal antibody that attaches to over-expressed HER2 receptors in HER2-positive breast cancer, is well known to improve survival, especially combined with chemotherapy. However, women given the drug have a tendency to develop brain metastases. Study leader Andrew Wardley (Christie Hospital NHS Trust, Manchester, UK) adds that their “much larger study would seem to confirm the association, although its exact nature remains unclear”. Wardley and colleagues assessed the medical records of 93 patients with HER2-positive breast cancer who were given trastuzumab to determine how many developed brain metastases after treatment had begun, and to see whether there were any clinical or pathological conditions that might be associated with the complication. As expected, trastuzumab was effective, with 57% of patients showing stable disease or a better response compared with those who did not receive the drug. After 1 year of treatment, however, 26·1% of patients had developed brain metastases. “We found that patients with visceral disease at the beginning of trastuzumab therapy were significantly more likely to develop brain metastases. We also saw some evidence that oestrogen-receptor status might be involved: 35% of the patients with oestrogen-receptornegative tumours developed brain metastases, compared with only 12% of those who were oestrogen-receptor positive”, says Wardley. However, no-one is claiming that trastuzumab is the cause of these
Living longer: nature of trastuzumab unclear.
treated with trastuzumab or other therapy combinations. That might help confirm whether prolonged survival is behind this association.” Adrian Burton
Racial and ethnic basis to breast tumours Black women diagnosed with breast carcinoma are more likely than their white counterparts to develop breast tumours with aggressive features, including alterations in the tumour suppressor gene P53, according to the results of a recent study. To investigate racial and ethnic differences in selected breast-tumour characteristics, Beth Jones, Yale University School of Medicine (New Haven, CT, USA), and colleagues retrieved and analysed the archived tumour-tissue samples of 145 black women and 177 white women who were diagnosed with breast cancer between 1987 and 1989 (Cancer, published online Aug 9, 2004; DOI: 10.1002/ cncr.20500). “In addition to confirming previous findings with regard to tumour stage, histological and nuclear grade, and hormone-receptor status, we also gleaned important new information about the frequency of molecular alterations in P53, HER2/NEU, and C-MET in black and white women with breast cancer”, Jones says. The researchers found that the frequency of alterations in P53 was four times higher in black women than in white women, even after adjustment
http://oncology.thelancet.com
for other tumour characteristics, disease stage, socioeconomic status, obesity, and selected lifestyle factors. Such alterations, which are reported to occur early in carcinogenesis and are associated with poor prognosis, might be responses to endogenous or environmental exposures that can vary between racial or ethnic groups, Jones comments. No significant racial or ethnic differences were seen in the overexpression of the oncogene HER2/ NEU or the proto-oncogene C-MET. Lisa Newman, University of Michigan Comprehensive Cancer Center (Ann Arbor, MI, USA), states that the findings underscore the importance of assessing variation in primary tumour biology in studies of disparities in cancer outcome. “The aetiology for survival disadvantages observed among black cancer patients is likely to be multifactorial and includes issues related to health-care access and delivery, as well as to cancer genetics”, she says. “For the hormonally-driven cancers, such as breast and prostate, the contribution of factors associated with primary tumour biology may be relatively stronger than previously appreciated.” Kathleen Wildasin
523