Very young women (<35 years) with operable breast cancer: features of disease at presentation

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Abstract

Breast cancer rarely occurs in young women. Our knowledge about disease presentation, prognosis and treatment effects are largely dependent upon older series. We evaluated biological features and stage at presentation for 1427 consecutive premenopausal patients aged < or = 50 years with first diagnosis of invasive breast cancer referred to surgery at the European Institute of Oncology from April 1997 to August 2000. A total of 185 patients (13%) were aged < 35 years ('very young') and 1242 (87%) were aged 35-50 years ('less young'). The expression of estrogen receptors (ER), progesterone receptors (PgR), presence of vascular invasion (VI), grading (G), expression of Ki-67, HER2/neu overexpression, pathological stage according to TNM staging system (pTNM), pathological tumor size and number of axillary lymph node involvement were evaluated. Compared with less young patients, the very young patient group had a higher percentage of tumors classified as ER negative (P < 0.001), PgR negative (P = 0.001), higher expression of Ki-67 > or = 20% of cells stained; 62.2% versus 53%, (P < 0.001), vascular or lymphatic invasion (48.6% versus 37.3%, P = 0.006), and pathological grade 3 (P < 0.0001). There was no difference between the two groups for pT, pathological tumor size (pN) and number of positive lymph nodes. We conclude that compared with less young premenopausal patients, very young women have a greater chance of having an endocrine-unresponsive tumor, and are more likely to present with a higher grade, more extensively proliferating and vessel invading disease. Pathological tumor size, nodal status and number of positive axillary lymph-nodes have a similar distribution among the younger and the older cohorts, thus not supporting previous data indicating more advanced disease in younger patients at diagnosis of operable disease.

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Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer.

J Peto, N. Collins, R Barfoot … (1999)

Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer. However, in an outbred population, the prevalence of BRCA1 and BRCA2 mutations in patients with breast cancer who were unselected for a family history of this disease has not been determined. Mutations in the BRCA1 and BRCA2 genes were detected in blood samples from two population-based series of young patients with breast cancer from Britain. Mutations were detected in 15 (5.9%) of 254 women diagnosed with breast cancer before age 36 years (nine [3.5%] in BRCA1 and six [2.4%] in BRCA2) and in 15 (4.1%) of 363 women diagnosed from ages 36 through 45 years (seven [1.9%] in BRCA1 and eight [2.2%] in BRCA2). Eleven percent (six of 55) of patients with a first-degree relative who developed ovarian cancer or breast cancer by age 60 years were mutation carriers, compared with 45% (five of 11) of patients with two or more affected first- or second-degree relatives. The standardized incidence ratio for breast cancer in mothers and sisters was 365 (five observed and 1.37 expected) for 30 mutation carriers and 199 (64 observed and 32.13 expected) for 587 noncarriers. If we assume recent penetrance estimates, the respective proportions of BRCA1 and BRCA2 mutation carriers are 3.1% and 3.0%, respectively, of patients with breast cancer who are younger than age 50 years, 0.49% and 0.84% of patients with breast cancer who are age 50 years or older, and 0.11% and 0.12% of women in the general population. Mutations in the BRCA1 and BRCA2 genes make approximately equal contributions to early-onset breast cancer in Britain and account for a small proportion of the familial risk of breast cancer.

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HER-2/neu gene amplification characterized by fluorescence in situ hybridization: poor prognosis in node-negative breast carcinomas.

Elizabeth Robinson, D Slamon, Jessica Marie Ross … (1997)

The HER-2/neu gene codes for a membrane receptor protein that is homologous, but distinct from the epidermal growth factor receptor. This investigation was performed to validate fluorescence in situ hybridization (FISH) as a sensitive and specific method for assessing HER-2/neu gene amplification in archival tissue and to test whether this alteration is associated with poor prognosis. HER-2/neu gene amplification was determined by FISH in 140 archival breast cancers, previously characterized for gene amplification by Southern hybridization or dot-blot hybridization, and for gene expression by Northern hybridization, Western immunoblot, or immunohistochemistry. A separate cohort of 324 node-negative breast cancers was assessed for amplification by FISH to determine the utility of HER-2/neu gene amplification. Relative to solid-matrix blotting procedures, FISH analysis of HER-2/neu gene amplification showed a sensitivity of 98% and a specificity of 100% in 140 breast cancers. Among patients treated by surgery only, the relative risks (relative hazard) of early recurrence (recurrent disease within 24 months of diagnosis), recurrent disease (at any time), and disease-related death were statistically significantly associated with amplification. The prognostic information contributed by HER-2/neu amplification was independent of the other markers studied. FISH was an alternative technique for determining gene amplification and had some distinct advantages over Southern hybridization. Our results demonstrate that HER-2/neu gene amplification in the absence of adjuvant therapy is an independent predictor of poor clinical outcome and is a stronger discriminant than tumor size. Women with small tumors that had gene amplification were at increased risk of recurrence and disease-related death.

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The relation between survival and age at diagnosis in breast cancer.

H O Adami, B. Malker, I Mahmutovic-Persson … (1986)

We analyzed the relation between age at diagnosis and relative survival (ratio of observed to expected survival) in 57,068 women in Sweden in whom breast cancer was diagnosed in 1960 to 1978 (about 98 percent of all cases). Women who were 45 to 49 years old had the best prognosis, with a relative survival exceeding that of the youngest patients (less than 30 years) by 7.6 to 12.9 percent at different periods of observation. Relative survival declined markedly after the age of 49--particularly in women aged 50 to 59--and the oldest women (greater than 75) had the worst rate. The difference in relative survival between those older than 75 and those 45 to 49 increased from 8.6 percent at 2 years to 12.2, 20.3, and 27.5 percent after 5, 10, and 15 years of follow-up, respectively. The long-term annual mortality rate due to breast cancer approached 1 to 2 percent at the premenopausal ages but exceeded 5 percent throughout the period of observation in the oldest age group. An understanding of the biologic basis for the complex relation between age and prognosis might provide a better understanding of the natural history of breast cancer in women.