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Objective: To assess influence of stage at breast cancer diagnosis, tumour biology, and therapy on survival in contemporary times of better (neo-)adjuvant systemic therapy., Design: Prospective nationwide population based study., Method: Female primary breast cancer patients diagnosed between 1999 and 2012 (173,797). Participants were subdivided into two time cohorts on the basis of breast cancer diagnosis; 1999 through 2005 (n = 80,228) and 2006 through 2012 (n = 93,569). Main outcome measures were relative survival, compared between both cohorts, and the influence of traditional prognostic factors on overall mortality, analyzed with Cox regression for both cohorts separately., Results: Compared to 1999-2005 patients from 2006-2012 had smaller ( ≤ T1 65 vs. 60%; p < 0.001), more often lymph node negative (N0 68 vs. 65%; p < 0.001) tumours, but they received more chemotherapy, hormonal therapy, and targeted therapy (neo-adjuvant/adjuvant systemic therapy 60 vs. 53%; p < 0.001). Median follow-up was 9.8 years for 1999-2005 and 3.9 years for 2006-2012. Relative 5-years survival rate was 96% in 2006-2012, improved in all tumour and nodal stages compared to 1999-2005, and 100% in tumours ≤ 1 cm. With multivariable analyses, adjusted for age and tumour type, overall mortality decreased by surgery (especially breast conserving), radiotherapy and systemic therapies. Mortality increased with progressing tumour size in both cohorts (2006-2012 T1c vs. T1a HR 1.54, 95% CI 1.33 to 1.78), but without significant difference in invasive breast cancers until 1 cm (2006-2012 T1b vs. T1a HR 1.04, 95% CI 0.88 to 1.22), and independently with progressing number of positive lymph nodes (2006-2012 N1 vs. N0 HR 1.25, 95% CI 1.17 to 1.32)., Conclusion: Tumour stage at breast cancer diagnosis influences overall survival significantly also in the current era of effective systemic therapy. Early tumour stage at breast cancer diagnosis remains vital.

Objective: To determine the efficiency of surveillance among women with a high risk of breast cancer by semiannual breast examination and annual mammography., Setting: 'Dr. Daniel den Hoed' Cancer Centre, Rotterdam, the Netherlands., Design: Retrospective study., Method: In 1994 breast cancer was diagnosed in 92 patients: in 19 patients during surveillance (SU), in 48 referred because of symptoms (SY) and in 25 during the national screening programme (SC). The contributions of physical examination, mammography, ultrasound and fine needle aspiration cytology to the diagnosis were evaluated and the tumour stages in the 3 groups were compared., Results: The mean age was 53 years in the SU group, 51 years in the SY group and 64 years in the SC group. Breast cancer was detected by mammography only in 6%, 40% and 42% in the SY, SC and SU groups, respectively. 42% of patients had a family history of breast cancer in the SU group. Mammography failed to reveal malignancy in 25% of patients in the SU and SY groups combined. In women in the SU group 53% of breast cancers were: carcinoma in situ (Tis) or minimal invasive carcinoma (< 0.5 cm diameter; T1a). In patients with a family history of breast cancer 75% (6/8) were diagnosed in stages Tis or T1a, by surveillance. In the SY group 4% were Tis or T1a and 40% N1 + 2, in the SC group 8% and 20% respectively. 15.7% of the SU group had axillary lymph node metastases (N1) but only one of the 8 patients with a family history of breast cancer., Conclusions: Surveillance by palpation and mammography in women with a high risk of breast cancer is useful, because it detects this disease frequently at an early stage, when the prognosis is still good.

Recent discoveries in the field of molecular-genetic research make it possible to detect an increased genetic risk of tumours, because several genes are linked to hereditary forms of breast cancer. The breast cancer gene BRCA1, located on chromosome 17q, is quantitatively the most important gene so far. A BRCA1 gene mutation is estimated to occur in 1-3 per 1000 women in the general population, i.e. in about 10,000 women among the 4 million Dutch women aged 25-55 years. In this study experiences are described concerning oncologic, clinical-genetic and psychologic aspects in the first Dutch family in which a BRCA1-gene defect was detected with the corresponding hereditary breast/ovarian cancer syndrome. Of the relatives 88% participated in the genetic family study and 76% wished to be informed on the individual DNA-test results. From the first-degree relatives of the breast cancer patients 54% appeared to be gene mutation carrier. The detection of a gene mutation in a woman could make her decide to undergo preventive mastectomy and (or) ovariectomy, besides regular breast examination and mammography. Surgeons and radiotherapists, the group of doctors who treat primary breast cancer, have to anticipate more radical operations with regard to breasts in this selected group of (future) patients. Detection of the gene may also have consequences for family planning. Identification of carriers of the gene mutation can lead to a selection of women with increased risk of breast cancer. Primary or secondary preventive measures, early diagnostic management and regular examination may lead to a decrease in death from breast cancer.