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Background: The insulin-like growth factor (IGF)-binding proteins (IGFBPs) regulate the actions of the IGFs by influencing interactions between the IGFs and the IGF receptors. IGFBP-3, one of the six known species of IGFBPs, is the predominant IGFBP in serum and is expressed by breast cancer cells. Compared with estrogen receptor (PR)-positive samples, ER-negative breast cancer cell lines and tumors express higher levels of IGFBP-3. Therefore, expression of IGFBP-3 may be relevant in breast cancer biology, although it is unknown whether IGFBP-3 levels correlate with other breast cancer prognostic factors besides ER status. It is also not known how different methods used to measure IGFBP-3 in breast cancer correlate. Purpose: We measured IGFBP-3 messenger RNA (mRNA) and protein levels in breast tumors by different methods to test how these methods compare and to investigate the relationship between IGFBP-3 and breast cancer prognostic factors. Methods: We analyzed 40 human breast tumors and examined IGFBP-3 expression by ligand blot analysis, immunoblot analysis, immunoradiometric assay (IRMA), and ribonuclease protection assay. Another set of 40 breast tumors, selected according to ER and progesterone receptor (PR) status, S phase, and ploidy, was analyzed by IRMA. Results: In 26 (65%) of 40 samples in which RNA could be isolated, IGFBP-3 mRNA levels correlated with IGFBP-3 levels measured by IRMA (two-sided; P = .0001) but not with IGFBP-3 levels measured by ligand blot or immunoblot. Protein levels were highly correlated among all protein assays. Because the IRMA was more sensitive and accurate than the ligand blot and immunoblot assays, we used IRMA to examine IGFBP-3 levels in an additional 20 primary breast tumors with poor prognostic features (ER and PR negativity, high S phase, and aneuploidy) and in 20 tumors with good prognostic factors (opposite features). IGFBP-3 levels were threefold higher in tumors with poor prognostic features (mean [+ or -] standard deviation = 32.8 [+ or -] 25.2 versus 11.8 [+ or -] 9.7 ng/mg; two-sided; P = .003). Conclusions: These findings suggest that in human breast cancer, IGFBP-3 mRNA and protein levels are correlated and higher levels of IGFBP-3 are detectable in tumors with poor prognostic features. Implications: IGFBP-3 may be involved in the regulation of breast cancer cell growth. [J Natl Cancer Inst 1996;88:601-6]

BACKGROUND: Local recurrence following breastsparing surgery for breast cancer is no longer considered to be an ominous sign. Why this should be the case is not understood, and it poses a dilemma for the surgical oncologist. When does local recurrence represent an independent threat to survival? DATA SOURCES: I reviewed the few studies that have considered the size or tumor burden of locally persistent breast cancer, and the results of the Guy's Hospital Trials. CONCLUSIONS: Locally persistent breast cancer is seldom a risk to patient survival. The surgical literature is seriously deficient in its consideration of the tumor volume of locally persistent cancer. All available evidence suggests that a recurrent tumor is a risk only if its volume exceeds that of the original tumor. Patients appear to have a stable level of host defense against metastasizing tumor cells. Those who survive one breast cancer without developing distant disease can be expected to survive the local persistence of a similar volume of tumor. investigators should compare the size of each persistent lesion to the size of the patient's primary cancer. Excess deaths will occur only among patients whose persistent disease exceeds the volume of the primary. Am J Surg. 1996;171:445-448.

Background. Although smaller variant forms of estrogen receptor (ER) messenger RNA (mRNA) have been detected in breast tumors, neither their prevalence nor their prognostic significance have been evaluated. Similarly, TRPM-2 mRNA, the product of a gene induced principally during the onset of apoptosis, is present in mouse and human breast cancer cell lines, but whether it also occurs in primary breast tumors and is related to disease outcome is unknown. Methods. The relative expression and transcript size of ER mRNA and TRPM-2 mRNA in 126 primary breast tumors were measured by Northern analysis and compared with tumor grade, hormone receptor status, extent of tumor necrosis, and survival. Results. In ER-positive tumors, 64% of the tumors had only the normal 6.5 kb ER mRNA, an additional 9% had the normal plus smaller ER mRNA, and 2% had variant forms. Only 8% of ER-negative tumors had ER mRNA transcripts. There were significant relationships between the occurrence of ER mRNA and low tumor grade, ER-positive receptor status, and better survival. In contrast, TRPM-2 mRNA was found in only 17% of breast tumors, none of which could be grouped with respect to grade, hormone receptor status, or survival. Conclusions. The presence of smaller variant forms of ER mRNA either alone or in association with the normal ER transcript is not indicative of an unfavorable prognosis, whereas TRPM-2 mRNA occurs in many primary breast tumors, but has no apparent relationship to survival.

Background. A second primary tumor (SPT) in the breast is the most common one seen in clinical practice. There are conflicting reports regarding the incidence and survival of patients with SPT in the breast. Methods. To elucidate this, data on 139,932 patients with primary breast cancer, reported to the Surveillance, Epidemiology, and End Results Program between 1973 and 1986, were analyzed. Of these, 3431 patients had a contralateral metachronous breast cancer (interval, > 6 months). Results. Survival from the date of diagnosis of the metachronous breast tumors was compared with that of patients with single breast tumors, controlling for age at diagnosis, stage, race, and treatment. In the multivariate analysis, age and stage at diagnosis of first and second tumors were the only variables that significantly influenced survival. The survival of patients with localized SPT was similar to that of patients with a localized single breast tumor. Patients with regionally advanced SPT lived for a shorter time than did corresponding patients with only one tumor. Conclusions. Patients with single breast cancer were at increased risk of having a SPT in the breast. As a result, efforts for early detection by physical examination and mammography of survivors of single breast cancer are advocated because the survival of patients with a localized SPT in the breast is as good as that of those with a single localized tumor. Cancer 1993; 71:172-6.