Relationship between method of detection of breast cancer and stage of disease, method of treatment, and survival in women aged 40 to 49 years.

The optimal breast cancer screening program for women 40 to 49 years of age remains controversial. To help assess the value of screening mammography for this age group, we studied the relationship between the method of breast cancer detection and stage, therapy, and survival. Cases of breast cancer diagnosed at Sinai Hospital (Detroit, MI) between January 1985 and December 1994 were reviewed. A total of 181 cases involving 40- to 49-year-old women were available for analysis. The distribution of stage of disease significantly differed among the three methods of detection (P<0.0001). Breast-conserving surgery was more commonly performed in cases detected by screening mammography and clinical breast examination than in cases detected by breast self-examination (P = 0.001). Variation in the stage of disease resulted in improved survival for cases detected by screening mammography and clinical breast examination when compared with those detected by breast self-examination (P = 0.019). Women diagnosed with breast cancer between the ages of 40 and 49 years had earlier stage disease, were more likely to be treated with breast-conserving therapy, and had better survival if their disease was first recognized by screening mammography. Screening mammography has an important role for women of this age.

Axillary lymph node metastases associated with small invasive breast carcinomas.

BACKGROUND: Over the past 20 years the proportion of invasive breast carcinomas measuring < or = 1 cm has increased progressively. Information regarding the effect of clinical and histologic characteristics on the frequency of lymph node metastases associated with small invasive breast carcinomas is limited. METHODS: A review of Surveillance, Epidemiology, and End Results data was performed using cases diagnosed between January 1988 through December 1993. A total of 12,950 patients with invasive breast carcinomas measuring < or = 1 cm undergoing a resection of the primary tumor and an axillary lymph node dissection were included in this study. The effect of clinical and histologic characteristics on the frequency of lymph node metastases was reviewed. RESULTS: The frequency of lymph node metastases associated with T1a tumors was less than that observed from T1b tumors (9.6% vs. 14.3%; P < 0.001). Tumors with favorable histology (mucinous, papillary, and tubular carcinomas) had a lower frequency of lymph node metastases compared with all other histologic types (3.9% vs. 13.9%; P < 0.001). Increasing histologic grade was associated with an increased risk of lymph node metastases ranging from 7.8% in Grade 1 tumors to 21.0% in Grade 4 tumors (P < 0.001). Increasing patient age was associated with a progressively decreasing frequency of associated axillary lymph node metastases ranging from 22.6% in women age < 40 years to 10.2% in women age > or = 70 years (P < 0.001). CONCLUSIONS: Cases in which an axillary lymph node dissection can be avoided are those with an associated frequency of lymph node metastases < or = 5%, including T1a and T1b mucinous and tubular carcinomas, T1a papillary carcinomas, and T1a Grade 1 carcinomas.

Triplex forming ability of a c-myc promoter element predicts promoter strength.

Most transcription factors are believed to bind promoter elements in the B-DNA conformation, wherein linear sequence determines specificity. However, there are promoter elements that can form complex structures such as intramolecular triplexes, and these structures may participate in the activity of these promoter elements. We have previously shown that a c-myc promoter element, termed the nuclease-sensitive element or NSE, can form tandem intramolecular triplexes of the H-DNA type and has a repeating sequence motif (ACCCTCCCC)4. The NSE was mutated and examined for transcriptional activity and for intra- and intermolecular triplex forming ability. The transcriptional activity of mutant NSEs can be predicted by the element's ability to form H-DNA and not by repeat number, position, or the number of mutant base pairs. DNA may therefore be a dynamic participant in the transcription of the c-myc gene.

The identification of a tandem H-DNA structure in the c-myc nuclease sensitive promoter element.

Previous studies have shown that the c-myc nuclease sensitive element (NSE) is capable of forming H-DNA in vitro. The NSE sequence exhibits strong purine/pyrimidine strand asymmetry. To study the NSE further, we have isolated the element from other c-myc sequences and have shown that the NSE alone is sufficient for the formation of H-DNA in supercoiled plasmids. We also show that the NSE forms a complex structure containing both H-y3 and H-y5 H-DNA. We term this structure tandem H-DNA.

Base and conformational specificity of an amine modification of DNA.

We have investigated the site and conformational preference of the reaction of a formaldehyde/amine reagent with DNA. Previous investigations of this laboratory have established that this reagent will react with native DNA, placing a positively charged amine moiety on the duplex that will survive exhaustive dialysis. The resulting adduct is duplex and base stacked in character, possessing B backbone geometry with a higher average winding angle and exhibiting remarkable stability with respect to the A-form, Z-form, or the single-strand denaturated species. In this current investigation, we have found that the stability of the adduct is dramatically reduced if the DNA is converted to mononucleotides, thus obviating the usual approach of nuclease digestion and chromatography for the identification of the modified nucleotides. Using indirect approaches, we have established that the reactive site that survives removal of the equilibrium concentrations of CH2O and amine is the exocyclic amino group of the guanine bases. This conclusion is based on (1) the positive correlation between GC content and the extent of adduct formation under standard reaction conditions (27 degrees C, 0.63M CH2O, 0.007M n-butylamine, pH 7); (2) decreases in the level of substitution of amine in DNA, which has this site blocked by trinitrobenzene modification; and (3) failure of poly(dI-dC) to retain amine upon dialysis. Raman spectra of the derivatized poly(dG-dC) show enhanced 2'-endo B character, with no marked shifts in the position of any of the lines, indicating the absence of any ring structures involving the N7 and the 06 of G. In standard reaction mixtures, other sites may react but this phenomenon appears to be minimal under conditions that do not favor fluctuational opening of base pairs. In the latter case, excess loading of amine on high GC content polymers produces a CD spectrum that is similar to one produced by poly(dA-dT) in the "X"-form [M. Vorlickova, E. Minyat, and J. Kypr (1984) Biopolymers 23, 1-4]. This conformation is lost, however, upon removal of excess reagents by dialysis and cannot be reestablished, in the absence of unbound amine and formaldehyde. The reaction is specific for the B-form of polynucleotides as demonstrated by the failure of poly(dG-m5dC) in the stable Z-form to exhibit substantial reaction. The B-form of this polymer will react readily with the retention of 0.23 moles amine/mole nucleotide under our standard reaction conditions.(ABSTRACT TRUNCATED AT 400 WORDS)