Population‐based analysis of occult primary breast cancer with axillary lymph node metastasis

BACKGROUND:

Single‐institution data suggest that treatment with radiation and axillary lymph node dissection (ALND) may be an appropriate alternative to mastectomy for T0N+ breast cancer. Population‐based multi‐institutional data supporting this approach are lacking.

METHODS:

The cause‐specific survival (CSS) and overall survival (OS) of women with T0N+M0 ductal, lobular, or mixed breast cancer in the Surveillance, Epidemiology, and End Results database from 1983 to 2006 were analyzed. Groups were defined as: 1) no ALND, mastectomy, or RT (observation); 2) ALND only; 3) mastectomy plus ALND with or without postmastectomy radiation (Mast); and 4) breast‐conserving therapy (BCT) with ALND and radiation (BCT).

RESULTS:

In total, 750 of 770,030 patients with breast cancer had T0N+M0 disease (incidence, 0.10%), and 596 of those patients underwent ALND (79.5%). Patients who underwent Mast or BCT (n = 470) had a 10‐year OS rate of 64.9% compared with 58.5% for patients who underwent ALND only (n = 126; P = .02) and 47.5% for patients who underwent observation only (n = 94; P = .04). The 10‐year CSS rate was 75.7% for patients who underwent BCT versus 73.9% for patients who underwent Mast (P = .55). In multivariate analysis of CSS for patients who underwent Mast or BCT, the following factors were correlated with an unfavorable outcome: positive estrogen receptor status (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.24‐0.96; P = .04), ≥10 positive lymph nodes (HR, 5.7; 95%CI, 2.4‐13.4; P ≤ .01), and <10 resected lymph nodes (HR, 42.9; 95%CI, 1.2‐7.1; P = .02). Mast did not improve CSS compared with BCT (HR, 1.09; 95%CI, 0.57‐2.1; P = .79).

CONCLUSIONS:

Definitive locoregional treatment with either Mast or BCT improved the outcome of patients with T0N+breast cancer, and no difference in survival was observed between the treatments. Cancer 2010. © 2010 American Cancer Society.     

Recurrence and survival rates in British and Japanese women with breast cancer

The biology of breast cancer in Japan appears to be changing in that, while post-menopausal Japanese patients have a better prognosis than comparable British women, no differences in recurrence or survival rates can now be found in pre-menopausal patients.     

Migration from low‐ to high‐risk countries: a qualitative study of perceived risk of breast cancer and the influence on participation in mammography screening among migrant women in Denmark

Migrants are less likely to participate in mammography screening programmes compared with local‐born populations in Europe. We explored perceptions of breast cancer risk and the influence on participation in mammography screening programmes among migrant women born in countries with low incidence rates of breast cancer. We conducted eight individual interviews and six group interviews including a total of 29 women aged 50–69 years living in Copenhagen, Denmark. Women were migrants born in Somalia, Turkey, Pakistan or Arab countries. Phenomenological analysis was used. Breast cancer was perceived to be caused by multiple factors, including genetics, health behaviour, stress, fertility and breastfeeding. Some women perceived breast cancer to be more prevalent in Denmark as compared with their country of birth, and perceived their risk of developing breast cancer to increase with length of stay in Denmark. Although most women agreed on the relevance of mammography screening, other cancers, chronic and infectious diseases and mental health problems were mentioned as equally or more important to target in public health programmes. A life course perspective comprising previous and current circumstances in country of birth as well as immigration country is important for understanding and influencing the screening behaviour of migrants.     

DNA methylation variations in familial female and male breast cancer

In total, ~25% of familial breast cancer (BC) is attributed to germline mutations of the BRCA1 and BRCA2 genes, while the rest of the cases are included in the BRCAX group. BC is also known to affect men, with a worldwide incidence of 1%. Epigenetic alterations, including DNA methylation, have been rarely studied in male breast cancer (MBC) on a genome-wide level. The aim of the present study was to examine the global DNA methylation profiles of patients with BC to identify differences between familial female breast cancer (FBC) and MBC, and according to BRCA1, BRCA2 or BRCAX mutation status. The genomic DNA of formalin-fixed paraffin-embedded tissues from 17 women and 7 men with BC was subjected to methylated DNA immunoprecipitation and hybridized on human promoter microarrays. The comparison between FBC and MBC revealed 2,846 significant differentially methylated regions corresponding to 2,486 annotated genes. Gene Ontology enrichment analysis revealed molecular function terms, such as the GTPase superfamily genes (particularly the GTPase Rho GAP/GEF and GTPase RAB), and cellular component terms associated with cytoskeletal architecture, such as ‘cytoskeletal part’, ‘keratin filament’ and ‘intermediate filament’. When only FBC was considered, several cancer-associated pathways were among the most enriched KEGG pathways of differentially methylated genes when the BRCA2 group was compared with the BRCAX or BRCA1+BRCAX groups. The comparison between the BRCA1 and BRCA2+BRCAX groups comprised the molecular function term ‘cytoskeletal protein binding’. Finally, the functional annotation of differentially methylated genes between the BRCAX and BRCA1+BRCA2 groups indicated that the most enriched molecular function terms were associated with GTPase activity. In conclusion, to the best of our knowledge, the present study was the first to compare the global DNA methylation profile of familial FBC and MBC. The results may provide useful insights into the epigenomic subtyping of BC and shed light on a possible novel molecular mechanism underlying BC carcinogenesis.     

Racial and ethnic disparities in breast cancer rates by age: NAACCR Breast Cancer Project

Summary Objective. To examine age-specific rates of breast cancer incidence among racial and ethnic groups in the United States.Methods. Subjects were 363,801 women diagnosed with invasive breast cancer diagnosed during 1994–1998 and reported in the North American Association of Central Cancer Registries (NAACCR) data set. Variables analyzed included race, ethnicity, 5-year age group (from 10 years through 85+ years), and stage at time of diagnosis (localized, regional, distant). Incidence rates per 100,000 women were calculated for each 5-year age group and stratified by stage. Rate ratios and 95% confidence intervals were calculated by comparing each racial group with whites and Hispanics with non-Hispanics.Results. Black women experience significantly higher breast cancer incidence up to the age of 40 years and significantly lower incidence after age 50 compared with white women of the same ages. This is called the ‘crossover’ effect. This shifting burden of higher incidence occurs at ages 35–39 for localized stage and at ages 55–59 for regional stage. For distant stage, black women of all ages experience higher incidence compared with white women. Similar crossover effects do not exist for American Indian (AI) or Asian/Pacific Islander (API) women compared with white women. Both AI and API women have significantly lower incidence of breast cancer compared with white women, and Hispanic women have significantly lower incidence compared with non-Hispanic women.Conclusions. This study highlights racial and ethnic differences in breast cancer incidence rates among US women. The crossover effect between black and white women, particularly the lower incidence of localized stage disease diagnosed in older black women, is a significant phenomenon that may be associated with screening practices, and has implications for public health planning and cancer control initiatives to reduce racial/ethnic disparities.     

Heterogeneity of breast cancer risk within the South Asian female population in England: a population-based case-control study of first-generation migrants

South Asian women in England have a lower breast cancer risk than their English-native counterparts, but less is known about variations in risk between distinct South Asian ethnic subgroups. We used the data from a population-based case-control study of first-generation South Asian migrants to assess risks by ethnic subgroup. In all, 240 breast cancer cases, identified through cancer registries, were individually matched on age and general practitioner to two controls. Information on the region of origin, religious and linguistic background, and on breast cancer risk factors was obtained from participants. Breast cancer odds varied significantly between the ethnic subgroups (P=0.008), with risk increasing in the following order: Bangladeshi Muslims (odds ratio (OR) 0.33, 95% confidence interval (CI): 0.10, 1.06), Punjabi Hindu (OR 0.59, 95% CI: 0.33, 1.27), Gujarati Hindu (1=reference group), Punjabi Sikh (OR 1.23, 95% CI: 0.72, 2.11) and Pakistani/Indian Muslims (OR 1.76, 95% CI: 1.10, 2.81). The statistically significant raised risk in Pakistani/Indian Muslims increased with adjustment for socioeconomic and reproductive risk factors (OR 2.12, 95% CI: 1.25, 3.58), but was attenuated, and no longer significant, with further adjustment for waist circumference and intake of nonstarch polysaccharides and fat (OR 1.49, 95% CI: 0.85, 2.63). These findings reveal differences in breast cancer risk between South Asian ethnic subgroups, which were not fully explained by reproductive differences, but were partly accounted for by diet and body size.     

Incidence of cancer of the lung stomach,breast, and cervix in the USSR: pattern and trends

The most frequent fatal malignant tumors in the Soviet Union are cancers of the lung, stomach, breast, and cervix uteri. From incidence statistics and population estimates provided by the Department of Statistics of the Ministry of Health, age-adjusted incidence rates for the period 1971–87, using the World standard population, have been computed for the USSR as a whole and for each of the 15 Soviet republics. For six republics believed to have the highest quality of data and relatively homogeneous populations, time-trends are examined over the period. There is important geographical variation in the incidence of malignant tumors in the Soviet Union. The differences between high and low incidence areas are four-fold for cancer of the lung and stomach, three-fold for cancer of the breast and two-fold for cancer of the cervix. Overall in the six republics for which time-trends are examined, cancers of the lung and breast have increased, cancers of the stomach and cervix have decreased. There are some variations in specific age groups in some republics.The authors are in the Institute of Carcinogenesis, Department of Epidemiology of the All-Union Cancer Research Centre of the Academy of Medical Sciences of the USSR, Moscow. Address reprint requests to Dr Zaridze at Kashirskoye sh. 24, Moscow 115478, USSR.     

Ethnicity and outcome of young breast cancer patients in the United Kingdom: the POSH study

Background:

Black ethnic groups have a higher breast cancer mortality than Whites. American studies have identified variations in tumour biology and unequal health-care access as causative factors. We compared tumour pathology, treatment and outcomes in three ethnic groups in young breast cancer patients treated in the United Kingdom.

Methods:

Women aged ⩽40 years at breast cancer diagnosis were recruited to the POSH national cohort study (MREC: 00/06/69). Personal characteristics, tumour pathology and treatment data were collected at diagnosis. Follow-up data were collected annually. Overall survival (OS) and distant relapse-free survival (DRFS) were assessed using Kaplan–Meier curves, and multivariate analyses were performed using Cox regression.

Results:

Ethnicity data were available for 2915 patients including 2690 (91.0%) Whites, 118 (4.0%) Blacks and 87 (2.9%) Asians. Median tumour diameter at presentation was greater in Blacks than Whites (26.0 mm vs 22.0 mm, P=0.0103), and multifocal tumours were more frequent in both Blacks (43.4%) and Asians (37.0%) than Whites (28.9%). ER/PR/HER2-negative tumours were significantly more frequent in Blacks (26.1%) than Whites (18.6%, P=0.043). Use of chemotherapy was similarly high in all ethnic groups (89% B vs 88.6% W vs 89.7% A). A 5-year DRFS was significantly lower in Blacks than Asians (62.8% B vs 77.0% A, P=0.0473) or Whites (62.8 B% vs 77.0% W, P=0.0053) and a 5-year OS for Black patients, 71.1% (95% CI: 61.0–79.1%), was significantly lower than that of Whites (82.4%, 95% CI: 80.8–83.9%, W vs B: P=0.0160). In multivariate analysis, Black ethnicity had an effect on DRFS in oestrogen receptor (ER)-positive patients that is independent of body mass index, tumour size, grade or nodal status, HR: 1.60 (95% CI: 1.03–2.47, P=0.035).

Conclusion:

Despite equal access to health care, young Black women in the United Kingdom have a significantly poorer outcome than White patients. Black ethnicity is an independent risk factor for reduced DRFS particularly in ER-positive patients.     

Genetic variations in vitamin D‐related pathways and breast cancer risk in African American women in the AMBER consortium

Studies of genetic variations in vitamin D‐related pathways and breast cancer risk have been conducted mostly in populations of European ancestry, and only sparsely in African Americans (AA), who are known for a high prevalence of vitamin D deficiency. We analyzed 24,445 germline variants in 63 genes from vitamin D‐related pathways in the African American Breast Cancer Epidemiology and Risk (AMBER) consortium, including 3,663 breast cancer cases and 4,687 controls. Odds ratios (OR) were derived from logistic regression models for overall breast cancer, by estrogen receptor (ER) status (1,983 ER positive and 1,098 ER negative), and for case‐only analyses of ER status. None of the three vitamin D‐related pathways were associated with breast cancer risk overall or by ER status. Gene‐level analyses identified associations with risk for several genes at a nominal p ≤ 0.05, particularly for ER‐ breast cancer, including rs4647707 in DDB2. In case‐only analyses, vitamin D metabolism and signaling pathways were associated with ER‐ cancer (pathway‐level p = 0.02), driven by a single gene CASR (gene‐level p = 0.001). The top SNP in CASR was rs112594756 (p = 7 × 10^?5, gene‐wide corrected p = 0.01), followed by a second signal from a nearby SNP rs6799828 (p = 1 × 10^?4, corrected p = 0.03). In summary, several variants in vitamin D pathways were associated with breast cancer risk in AA women. In addition, CASR may be related to tumor ER status, supporting a role of vitamin D or calcium in modifying breast cancer phenotypes.     

Matriptase‐2 gene (TMPRSS6) variants associate with breast cancer survival,and reduced expression is related to triple‐negative breast cancer

Matriptase‐2 (TMPRSS6) has been identified as a breast cancer risk factor. Here, we examined relationships between TMPRSS6 genetic variations and breast cancer risk and survival, and determined the gene and protein expressions in breast tumors and assessed their clinical importance. Thirteen TMPRSS6 polymorphisms were genotyped in 462 invasive breast cancer cases and 458 controls. Gene expression was analyzed from 83 tumors and protein expression from 370 tumors. We then assessed the statistical significance of associations among genotypes, clinicopathological characteristics and survival. The TMPRSS6 variant rs2543519 was associated with breast cancer risk (p = 0.032). Multivariate analysis showed that four variants had effects on survival—rs2543519 (p = 0.017), rs2235324 (p = 0.038), rs14213212 (p = 0.044) and rs733655 (p = 0.021)—which were used to create a group variable that was associated with poorer prognosis correlating with more alleles related to reduced survival (p = 0.006; risk ratio, 2.375; 95% confidence interval, 1.287–4.382). Low gene expression was related to triple‐negative breast cancer (p = 0.0001), and lower protein expression was detected in undifferentiated (p = 0.019), large (p = 0.014) and ductal or lobular tumors (p = 0.036). These results confirm the association of TMRRSS6 variants with breast cancer risk and survival. Matriptase‐2 levels decrease with tumor progression, and lower gene expression is seen in poor‐prognosis‐related triple‐negative breast cancers. Our study is the first to show that matriptase‐2 gene variants are related to breast cancer prognosis, supporting matriptase‐2 involvement in tumor development.     

Night work and breast cancer: A population‐based case–control study in France (the CECILE study)

Night work involving disruption of circadian rhythm was suggested as a possible cause of breast cancer. We examined the role of night work in a large population‐based case‐control study carried out in France between 2005 and 2008. Lifetime occupational history including work schedules of each night work period was elicited in 1,232 cases of breast cancer and 1,317 population controls. Thirteen percent of the cases and 11% of the controls had ever worked on night shifts (OR = 1.27 [95% confidence interval = 0.99–1.64]). Odds ratios were 1.35 [1.01–1.80] in women who worked on overnight shifts, 1.40 [1.01–1.92] in women who had worked at night for 4.5 or more years, and 1.43 [1.01–2.03] in those who worked less than three nights per week on average. The odds ratio was 1.95 [1.13–3.35] in women employed in night work for >4 years before their first full‐term pregnancy, a period where mammary gland cells are incompletely differentiated and possibly more susceptible to circadian disruption effects. Our results support the hypothesis that night work plays a role in breast cancer, particularly in women who started working at night before first full‐term pregnancy.     

Health‐related quality of life in long‐term breast cancer survivors

BACKGROUND:

The Survivor's Health and Reaction (SHARE) study examined health‐related quality of life (HRQL) in breast cancer patients who had participated in Cancer and Leukemia Group B Trial 8541 from 1985 to 1991.

METHODS:

In total, 245 survivors (78% of eligible patients) who were 9.4 to 16.5 years postdiagnosis (mean, 12.5 years postdiagnosis) completed HRQL surveys relating to 5 domains. Analyses examined HRQL domains according to 3 different chemotherapy dose levels that were administered in the original treatment trial: low‐dose cyclophosphamide, doxorubicin, and fluorouracil (CAF) at 300 mg/m², 30 mg/m², and 300×2 mg/m², respectively, over 4 cycles; standard‐dose CAF at 400 mg/m², 40 mg/m², and 400×2 mg/m², respectively, over 6 cycles; and high‐dose CAF at 600 mg/m², 60 mg/m² and 600×2 mg/m², respectively, over 4 cycles.

RESULTS:

In univariate analyses, a statistically significant difference was observed on the Medical Outcomes Study 36‐item short form Physical Role Functioning subscale by treatment group, with lower mean scores in the standard treatment arm (mean, 65.05) compared with mean scores in the low‐dose arm (mean, 74.66) and the high‐dose arm (mean, 84.94; P.0001). However, multivariate analysis revealed that treatment arm no longer was statistically significant, whereas the following factors were associated with decreased physical role functioning: age ≥60 years (odds ratio [OR], 3.55; P = .006), increased comorbidity interference total score (OR, 1.64; P = .005), lower vitality (OR, 1.05; P = .0002), and increased menopausal symptoms (OR, 1.04 P = .02).

CONCLUSIONS:

At 9.4‐16.5 years after their original diagnosis, differences in physical role functioning among breast cancer survivors who had received 3 different dose levels of chemotherapy were explained by clinical and demographic variables, such as age, fatigue, menopausal symptoms, and comorbidities. Prospective studies are needed to further assess the role of these factors in explaining HRQL and physical role functioning among long‐term survivors. Cancer 2009. © 2009 American Cancer Society.     

An international comparison of male and female breast cancer incidence rates

Global international trends in female breast cancer incidence have been described previously but no comparable analysis of male breast cancer incidence rates has been conducted. We obtained male and female case and population data using Cancer Incidence in Five Continents (CI5). We calculated age‐adjusted, sex‐specific incidence rates and female‐to‐male incidence rate ratios (FMIRRs) and compared trends of such for the period 1988–2002. This analysis included 8,681 male breast cancer cases and 1.14 million female breast cancer cases. The highest male incidence rate was observed in Israel at 1.24 per 100,000 man‐years, and the highest female incidence rate was observed in the United States at 90.7 per 100,000 woman‐years. The lowest incidence rates for males (0.16) and females (18.0) were observed in Thailand. In general, male breast cancer incidence trends were variable; a minority of countries displayed evidence for an increase. In contrast, female incidence rates have been increasing in a majority of countries. The Pearson correlation coefficient (r) for male and female breast cancer incidence rates by country during 1988–2002 was 0.69. Male breast cancer rates were generally less than 1 per 100,000 man‐years, in contrast to the much higher rates of female breast cancer, providing for an overall FMIRR of 122. The differences in both incidence rates and time trends between males and females may reflect sex differences in underlying risk factors, pathogenesis, and/or overdiagnosis. Conversely, the high correlation between male and female breast cancer incidences may indicate that both sexes share some common risk factors for breast cancer.     

Medium‐dose‐rate brachytherapy for cancer of the cervix: Preliminary results of a designed schedule

Aim: This retrospective analysis aims to report results from patients with cervical cancer treated by external beam radiation (EBR) with telecobalt and medium‐dose‐rate (MDR) brachytherapy and to establish the magnitude of brachytherapy dose reduction. Methods: Between June 2003 and September 2005, 77 patients with histological diagnosis of cervical carcinoma were treated with cobalt for external beam radiation, followed by one or two insertions of MDR with a dose rate from 220 ± 10 cGy/h. Median dose of EBR at whole pelvis was 50 Gy and the planned MDR schedule consisted of 1 or 2 insertions with 10–12 Gy to point A. Results: 77 patients were followed for median of 15 months (range: 1–33 months). Local control was achieved in 63 patients 81.8%. Local failure and overall failure rates were 11.7% and 19.5%, respectively. Overall incidence of rectal and bladder complication was 9.0% (7/77) and 7.8% (6/77), respectively. Conclusion: Results of this series suggest that use of telecobalt for EBR together with MDR brachytherapy with a dose reduction around 20% in comparison with low‐dose‐rate (LDR) brachytherapy can be an acceptable technique, especially in developing countries.     

A case of breast cancer metastasizing to cervix after resection of pancreatic metastasis

A case of breast cancer that metastasized to the cervix 10 years and 8 months after mastectomy is reported. The patient had undergone pancreaticoduodenectomy due to solitary metastasis to the head of the pancreas 4 years previously. The cervical metastasis was associated with abnormal genital bleeding. After pancreaticoduodenectomy the serum levels of CEA, CA15-3 and NCC-ST-439, which are markers of breast cancer, were within normal limits, but the serum level of CA15-3 had increased month by month. The patient had abnormal genital bleeding and presented to the department of gynecology at our hospital. The tumor was in the cervix, bled easily and 2.5x2.0 cm in size on ultrasonography. It was thought to be carcinoma of the cervix, but biopsy revealed the tumor to be an adenocarcinoma pathologically and CA15-3 was immunohistochemically demonstrated in the resected specimen, similar to lobular carcinoma of the breast. Abdominal CT scan revealed involvement of the ovaries and uterus, prompting hysterectomy with bilateral oophorectomy. After discharge, she received chemoendocrine therapy. However, she subsequently died due to peritoneal carcinomatosis.