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Surrogates are just surrogates, but helpful just the same

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A surrogate end-point biomarker (SEB) may broadly be defined as a predictive measure of a future outcome... Optimally, both risk and response SEBs should be prospectively validated in a clinical trial in which the nonsurrogate outcome is also being evaluated... Perhaps the greatest need for surrogate biomarkers is in the prevention setting, where the traditionally measured outcome of cancer occurs infrequently and only after a long latent period... Biomarkers that accurately predict short-term risk are needed in order to avoid treating healthy women with drugs tthat most do not need in order to benefit a few... The disadvantages are that it is negatively correlated with some risk factors, including age and obesity, and may be negatively correlated with free oestradiol... There is substantial technical and interpretive variance, and it is unclear whether effective agents such as tamoxifen and raloxifene reduce density in postmenopausal women over 55 years old... Cuzick and coworkers suggested that reduction in density is associated with only one-third of the risk reduction resulting from tamoxifen administration... The advantages of breast tissue sampling by RPFNA for risk and response biomarkers is that it provides a direct assessment of precancerous change as well as tissue for other response and predictive markers such as Ki-67 and oestrogen receptor (ER), and there is minimal discomfort... Consequently, changes in Ki-67 and ER expression were explored as end-points for phase II trials with antihormonal agents in our trial of letrozole in high-risk women on HRT... Postmenopausal women produce the majority of breast oestrogen locally via aromatase and sulfatase and aromatase activity is increased in precancerous breast tissue... We found a significant decrease in benign breast tissue Ki-67 (mean 5.1% at baseline and 1.5% after 6 months of letrozole) in 42 high-risk women on a stable dose of hormone replacement... Modulation of an individual surrogate response biomarker is likely to be dramatically influenced by agent, menopause status and baseline characteristics of the cohort (Table 1)... Biomarkers are extremely valuable in initial testing of new strategies, particularly in prevention... However, it is important to understand how the agents may differentially modulate risk biomarkers, so that an effective agent is not discarded because it does not favourably modulate all risk biomarkers.

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Surrogate response biomarkers will guide neoadjuvant treatment. ER, oestrogen receptor; pCR, pathological complete response; PR, progesterone receptor; Rx, treatment.
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Figure 1: Surrogate response biomarkers will guide neoadjuvant treatment. ER, oestrogen receptor; pCR, pathological complete response; PR, progesterone receptor; Rx, treatment.

Mentions: In the neoadjuvant setting, a low Ki-67 a few weeks after initiation of treatment and pathological response after several months of treatment both predict long-term disease-free survival [3-5]. Both biomarkers are currently used in the research setting, and pathological stage after neoadjuvant treatment is used clinically to estimate distant disease-free survival. It is probable that, in the near future, early reduction in breast proliferation will be used along with clinical indices to determine whether to switch antihormonal or chemotherapeutic treatment during the neoadjuvant period. Pathological response after neoadjuvant chemotherapy will also probably be used to determine whether to administer additional chemotherapy adjuvantly to women with hormone receptor negative tumours (Figure 1).


Surrogates are just surrogates, but helpful just the same
Surrogate response biomarkers will guide neoadjuvant treatment. ER, oestrogen receptor; pCR, pathological complete response; PR, progesterone receptor; Rx, treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2230526&req=5

Figure 1: Surrogate response biomarkers will guide neoadjuvant treatment. ER, oestrogen receptor; pCR, pathological complete response; PR, progesterone receptor; Rx, treatment.
Mentions: In the neoadjuvant setting, a low Ki-67 a few weeks after initiation of treatment and pathological response after several months of treatment both predict long-term disease-free survival [3-5]. Both biomarkers are currently used in the research setting, and pathological stage after neoadjuvant treatment is used clinically to estimate distant disease-free survival. It is probable that, in the near future, early reduction in breast proliferation will be used along with clinical indices to determine whether to switch antihormonal or chemotherapeutic treatment during the neoadjuvant period. Pathological response after neoadjuvant chemotherapy will also probably be used to determine whether to administer additional chemotherapy adjuvantly to women with hormone receptor negative tumours (Figure 1).

View Article: PubMed Central - HTML

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

A surrogate end-point biomarker (SEB) may broadly be defined as a predictive measure of a future outcome... Optimally, both risk and response SEBs should be prospectively validated in a clinical trial in which the nonsurrogate outcome is also being evaluated... Perhaps the greatest need for surrogate biomarkers is in the prevention setting, where the traditionally measured outcome of cancer occurs infrequently and only after a long latent period... Biomarkers that accurately predict short-term risk are needed in order to avoid treating healthy women with drugs tthat most do not need in order to benefit a few... The disadvantages are that it is negatively correlated with some risk factors, including age and obesity, and may be negatively correlated with free oestradiol... There is substantial technical and interpretive variance, and it is unclear whether effective agents such as tamoxifen and raloxifene reduce density in postmenopausal women over 55 years old... Cuzick and coworkers suggested that reduction in density is associated with only one-third of the risk reduction resulting from tamoxifen administration... The advantages of breast tissue sampling by RPFNA for risk and response biomarkers is that it provides a direct assessment of precancerous change as well as tissue for other response and predictive markers such as Ki-67 and oestrogen receptor (ER), and there is minimal discomfort... Consequently, changes in Ki-67 and ER expression were explored as end-points for phase II trials with antihormonal agents in our trial of letrozole in high-risk women on HRT... Postmenopausal women produce the majority of breast oestrogen locally via aromatase and sulfatase and aromatase activity is increased in precancerous breast tissue... We found a significant decrease in benign breast tissue Ki-67 (mean 5.1% at baseline and 1.5% after 6 months of letrozole) in 42 high-risk women on a stable dose of hormone replacement... Modulation of an individual surrogate response biomarker is likely to be dramatically influenced by agent, menopause status and baseline characteristics of the cohort (Table 1)... Biomarkers are extremely valuable in initial testing of new strategies, particularly in prevention... However, it is important to understand how the agents may differentially modulate risk biomarkers, so that an effective agent is not discarded because it does not favourably modulate all risk biomarkers.

No MeSH data available.