Abstract
BackgroundProgranulin (PGRN) is considered to play an important role in breast cancer tumorigenesis and in inhibiting tamoxifen-induced apoptosis. We aimed to determine whether PGRN levels are associated with breast cancer recurrence after curative surgery.Methodology/Principal FindingsWe evaluated the associations between preoperative serum PGRN levels and breast cancer recurrence in a cohort of 697 newly diagnosed breast cancer patients who underwent curative surgery between April 2001 and December 2004. The mean age ± standard deviation (SD) was 46±9.8 years, and all patients with hormone receptor (HR)-positive tumors received adjuvant tamoxifen therapy. At a median follow-up of 62.2 months (range, 2.9–98.2), 89 patients (12.8%) had experienced a recurrence and 51 patients (7.3%) had died. In the HR-positive group, serum PGRN levels were associated with recurrence according to the log-rank test for trend (p for trend = 0.049). There was no association between PGRN levels and recurrence in the HR-negative group (p for trend = 0.658). Adjusted hazard ratios, including possible confounders, revealed a linear relationship between serum PGRN levels and recurrence in the HR-positive group (p for trend = 0.049), and this association was further strengthened after excluding patients who had no lymph node metastasis (p for trend = 0.038).Conclusions/SignificanceSerum PGRN levels were clinically significant for predicting recurrence in patients with HR-positive breast cancer during adjuvant tamoxifen therapy.
Highlights
IntroductionBreast cancer has become the most common female cancer in many Asian and Western countries. [1] Estrogen receptor (ER) or progesterone receptor (PR)-positive breast cancers make up approximately three-quarters of all invasive breast cancers. [2] Because hormone receptor (HR) status is a powerful predictor of the efficacy of endocrine treatment, anti-hormonal therapy is given to HR-positive patients as adjuvant treatment after curative surgery or palliative treatment. HR-positivity in breast cancer is known to be a favorable prognostic factor, the total of number of recurrences is similar between HR-positive and HR-negative breast cancer patients because of the higher incidence of HR-positive breast cancer. [2] Biomarkers to predict recurrence or interventions to decrease the recurrence in HR-positive breast cancer are needed for use in conjunction with adjuvant hormonal therapy.Tamoxifen was the most common agent used in adjuvant settings until the recent clinical application of aromatase inhibitors
We demonstrated that preoperative serum PGRN levels in hormone receptor (HR)-positive breast cancer patients were associated with recurrence (p for trend,0.05), even after adjustment for possible mediating factors, including clinical, tumor and treatment variables
The outcome for breast cancer patients has been improved through the discovery of new agents such as HER2targeted agents and development of strategies such as tamoxifen followed by aromatase inhibitors for adjuvant hormonal therapy
Summary
Breast cancer has become the most common female cancer in many Asian and Western countries. [1] Estrogen receptor (ER) or progesterone receptor (PR)-positive breast cancers make up approximately three-quarters of all invasive breast cancers. [2] Because hormone receptor (HR) status is a powerful predictor of the efficacy of endocrine treatment, anti-hormonal therapy is given to HR-positive patients as adjuvant treatment after curative surgery or palliative treatment. HR-positivity in breast cancer is known to be a favorable prognostic factor, the total of number of recurrences is similar between HR-positive and HR-negative breast cancer patients because of the higher incidence of HR-positive breast cancer. [2] Biomarkers to predict recurrence or interventions to decrease the recurrence in HR-positive breast cancer are needed for use in conjunction with adjuvant hormonal therapy.Tamoxifen was the most common agent used in adjuvant settings until the recent clinical application of aromatase inhibitors. [2] Because hormone receptor (HR) status is a powerful predictor of the efficacy of endocrine treatment, anti-hormonal therapy is given to HR-positive patients as adjuvant treatment after curative surgery or palliative treatment. [2] Biomarkers to predict recurrence or interventions to decrease the recurrence in HR-positive breast cancer are needed for use in conjunction with adjuvant hormonal therapy. It was shown that five years of adjuvant tamoxifen treatment significantly reduced the recurrence and mortality rates in women with ER-positive or unknown tumors, and the benefit was largely irrespective of age or menopausal and nodal status. [4] As autocrine or paracrine growth factors increase, they may bypass the need for ER-mediated growth stimulation in human breast cancer cells, making anti-hormonal therapy ineffective. We aimed to determine whether PGRN levels are associated with breast cancer recurrence after curative surgery
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call