A large number of women survive a diagnosis of breast cancer. Knowledge of their risk of developing a new primary cancer is important not only in relation to potential side effects of their cancer treatment, but also in relation to the possibility of shared etiology with other types of cancer. A cohort of 525,527 women with primary breast cancer was identified from 13 population-based cancer registries in Europe, Canada, Australia and Singapore, and followed for second primary cancers within the period 1943-2000. We used cancer incidence rates of first primary cancer for the calculation of standardized incidence ratios (SIRs) of second primary cancer. Risk of second primary breast cancer after various types of nonbreast cancer was also computed. For all second cancer sites combined, except contralateral breast cancer, we found a SIR of 1.25 (95% CI 5 1.24-1.26) on the basis of 31,399 observed cases after first primary breast cancer. The overall risk increased with increasing time since breast cancer diagnosis and decreased by increasing age at breast cancer diagnosis. There were significant excesses of many different cancer sites; among these the excess was larger than 150 cases for stomach (SIR 5

Chemoradiation for locally recurrent or advanced disease may be an option for patients with a good performance status.

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Pooled data from 13 cancer registries show a 30% increased risk of second primary cancer after thyroid cancer and increased risks of thyroid cancer after various primary cancers. Although bias (detection, surveillance, misclassification) and chance may contribute to some of these observations, it seems likely that shared risk factors and treatment effects are implicated in many. When following up patients who have been treated for primary thyroid cancer, clinicians should maintain a high index of suspicion for second primary cancers.

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The objective of the study was to assess the risk of second primary cancers (SPCs) following a primary head and neck cancer (oral cavity, pharynx and larynx) and the risk of head and neck cancer as a SPC. The present investigation is a multicenter study from 13 population-based cancer registries. The study population involved 99,257 patients with a first primary head and neck cancer and contributed 489,855 person-years of follow-up. To assess the excess risk of SPCs following head and neck cancers, we calculated standardized incidence ratios (SIRs) by dividing the observed numbers of SPCs by the expected number of cancers calculated from accumulated person-years and the age-, sex-and calendar period-specific first primary cancer incidence rates in each of the cancer registries. During the observation period, there were 10,826 cases of SPCs after head and neck cancer. For all cancer sites combined, the SIR of SPCs was 1.86 (95% CI = 1.83-1.90) and the 20-year cumulative risk was 36%. Lung cancer contributed to the highest proportion of the SPCs with a 20-year cumulative risk of 13%. Excess second head and neck cancer risk was observed 10 years after diagnosis with lymphohaematopoietic cancers. The most common SPC following a first primary head and neck cancer was lung cancer. However, the highest excess of SPCs was in the head and neck region. These patterns were consistent with the notion that the pattern of cancer in survivors of head and neck cancer is dominated by the effect of tobacco smoking and alcohol drinking. ' 2008 Wiley-Liss, Inc.Key words: head and neck cancer; second cancer A significant improvement in locoregional control of head and neck squamous cell carcinoma has been seen over the last decades, due to the introduction of new surgical techniques, improved radiotherapy techniques and the use of chemotherapy. However, 5-year relative survival from head and neck cancer has not increased greatly over the period of 1985-1994. 1,2 One of the reasons for the lack of improvement in overall survival is the frequent development of second primary cancers (SPCs) that occur more often in head and neck cancer patients than in patients with cancers of other sites 3 and lead to poor prognosis. [4][5][6] Head and neck cancers (oral cavity, pharynx and larynx) comprise around 5% of all cancer cases worldwide and result in 6% of cancer deaths in men and 3% in women.7 SPCs after head and neck cancers are mostly found in the aerodigestive tract, including the lung and esophagus, which leads to a significant decrease in survival. 5 In contrast to the overall 5-year survival rate for head and neck cancer patients of approximately 50%, the 5-year survival rate in head and neck cancer patients who developed SPC was around 20% after the SPC was diagnosed. 4,5 The 5-year survival rates after SPC diagnosis were above 30% if the SPC was also a head and neck cancer and decreased to 8% if the SPC was outside the head and neck area.

We identified poor prognostic factors that may necessitate more aggressive treatment. The suggested staging system, incorporating primary tumour size, accurately predicted outcomes.

BACKGROUND Although delay to diagnosis after a breast screening abnormality causes anxiety, its effect on prognosis is unknown. METHODS Using pooled data from five Canadian organized breast cancer screening programs, the authors used unconditional logistic regression to evaluate the effect of delay to diagnosis on prognostic indicators among 4465 women with invasive breast carcinoma diagnosed in the ipsilateral breast within 3 years of an abnormal screen performed during 1990–1996. RESULTS Women with high‐suspicion screens (n = 1569) compared with those without (n = 2896) were more promptly investigated (median days from screen to diagnosis, 31 vs. 47; P ≤ 0.0001), had larger tumors (79.4% vs. 55.9% > 10 mm; P ≤ 0.0001), and were more likely to be lymph node positive (33.9% vs. 17.3%; P ≤ 0.0001). For delays beyond > 12 to ≤ 20 weeks, a linear trend of increased tumor size and lymph node positivity began to emerge. Controlling for suspicion, the authors found that odds ratios for tumor size greater than 10 mm were 0.9 (95% CI, 0.66–1.17), 1.2 (95% confidence interval [CI], 0.88–1.56), 1.5 (95% CI, 1.05–2.16), and 2.1 (95% CI, 1.15–3.86) for delays of > 12 to ≤ 20, > 20 to ≤ 52, > 52 to ≤ 104, and > 104 ≤ 156 weeks, respectively (ptrend ≤ 0.0001), compared with delays of > 4 to ≤ 12 weeks. Similarly, odds ratios for lymph node metastasis were 1.0 (95% CI, 0.67–1.42), 1.2 (95% CI, 0.84–1.69), 2.2 (95% CI, 1.48–3.15), and 3.2 (95% CI, 1.84–5.55) for the same time intervals (ptrend = 0.0033). CONCLUSIONS The authors' findings suggest that delays to diagnosis of asymptomatic breast carcinoma of 6 to 12 months are associated with progression of breast carcinoma as measured by increasing risk of lymph node metastases and larger tumor size. A policy of early recall rather than biopsy for low suspicion mammographic abnormalities may introduce delays of this magnitude. The tendency to more expediently investigate women with high‐suspicion, worse prognosis screens (suspicion bias) obscures whether delays shorter than 20 weeks also worsen prognostic indicators. Suspicion bias should be considered when interpreting the effect of delay on prognosis. Cancer 2002;94:2143–50. © 2002 American Cancer Society. DOI 10.1002/cncr.10453