Medline ® Abstracts for References 1-6

PURPOSE: Population-based estimates of the incidence of brain metastases are not generally available. The purpose of this study was to calculate population-based incidence proportions (IPs) of brain metastases from single primary lung, melanoma, breast, renal, or colorectal cancer.

PATIENTS AND METHODS: Patients diagnosed with single primary lung, melanoma, breast, renal, or colorectal cancer (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System (MDCSS) were used for analysis. IP of brain metastases by primary site and variable of interest (race, sex, age at diagnosis of primary cancer, and Surveillance, Epidemiology, and End Results [SEER]stage of primary cancer) was calculated with 95% CIs.

RESULTS: Total IP percentage (IP%) of brain metastases was 9.6% for all primary sites combined, and highest for lung (19.9%), followed by melanoma (6.9%), renal (6.5%), breast (5.1%), and colorectal (1.8%) cancers. Racial differences were seen with African Americans demonstrating higher IP% of brain metastases compared with other racial groups for most primary sites. IP% was significantly higher for female patients with lung cancer, and significantly higher for male patients with melanoma. The highest IP% of brain metastases occurred at different ages at diagnoses: age 40 to 49 years for primary lung cancer; age 50 to 59 years for primary melanoma, renal, or colorectal cancers; and age 20 to 39 for primary breast cancer. IP% significantly increased as SEER stage of primary cancer advanced for all primary sites.

CONCLUSION: Total IP% of brain metastases was lower than previously reported, and it varied by primary site, race, sex, age at diagnosis of primary cancer, and SEER stage of primary cancer.

The characteristics of brain metastases (BM) that develop after breast-conserving therapy (BCT) for early-stage breast cancer (BC) remain incompletely defined. We examined 1,434 consecutive patients with stage I/II invasive BC who received BCT from 1997 to 2006, 91 % of whom received adjuvant systemic therapy, according to BC subtype. Median follow-up was 85 months. Overall 5-year cumulative incidence of BM was 1.7 %; 0.1 % for luminal A, 3.3 % for luminal B, 3.2 % for luminal-HER2, 3.7 % for HER2, and 7.4 % for triple negative (TN). Women who developed BM were more likely at BC diagnosis to be younger (P < .0001) and have node-positive (P < .0001), grade 3 (P < .0001), hormone receptor-negative (P = .006), and HER2-positive (P = .01) tumors. Median time from BC diagnosis to BM was 51.4 months (range, 7.6-108 months), which was longer among luminal versus non-luminal subtypes (P = .0002; median, 61.4 vs. 34.5 months). Thirty-four percent of patients who developed distant metastases (DM) eventually developed BM. Median time from DM to BM was 12.8 months but varied by subtype, including 7.4 monthsfor TN, 9.6 months for luminal B, and 27.1 months for HER2. Eighty-one percent of all BM patients presented with neurologic symptoms. Median number of BM at diagnosis was two, and median BM size was 15 mm, with TN (27 mm) and luminal B (16 mm) exhibiting the largest median sizes. In conclusion, the risk of BM after BCT varies significantly by subtype. Given the large size and symptomatic presentation among luminal B and TN subtypes, earlier BM detection might improve quality of life or increase eligibility for non-invasive treatments including stereotactic radiosurgery. Women with DM from these two BC subtypes have a high incidence of BM with a short latency, suggesting an ideal target population for trials evaluating the utility of MRI screening.

Central nervous system (CNS) metastasis was noted in 309 patients of 1044 autopsy cases of breast carcinoma. The brain was involved in 193 cases, and cranial dura in 167 cases. In 82 cases, the cranial dura was the sole site of CNS involvement. Metastasis to the leptomeninges was found in 59 cases, and to the spinal cord and dura in 32 cases. Metastases to the infratentorial portion of the brain was almost as frequent as to the cerebrum. Forty-two percent of the brain metastasis were single lesions, which is similar to the frequency of solitary metastasis to the brain from malignant tumors as a whole. CNS metastasis occurred more frequently in younger patients than older patients, and the clinical course of these patients was shorter than for those patients without CNS metastasis. CNS metastasis developed in the late stage of the disease, and often was not recognized clinically. Only 31% of the cases were clinically diagnosed or suspected before death. A median survival of these patients after clinical diagnosis of CNS metastasis was 33 days. However, a significant improvement was noted in the clinical diagnosis and median survival in the latter half of the study period. Eleven patients lived for more than 1 year after diagnosis of CNS metastasis. Only 14% of the 309 patients died from CNS failure.

AIMS: Brain metastases from breast cancer are an uncommon initial presentation of metastatic breast cancer, but brain metastases commonly occur later in women's metastatic illness. The aims of this study were to document the type, frequency, and temporal occurrence of brain metastases from breast cancer as well as the survival of women with such metastases, and to attempt to identify a subgroup of women at high risk of brain metastases who may benefit from pre-emptive medical intervention.

MATERIALS AND METHODS: The radiological reports of all women presenting with metastases aged under 70 years who had subsequently died were examined. The type, frequency, temporal occurrence and survival with brain metastases were documented. Correlations were sought between the frequency of brain metastases and age at metastatic presentation, tumour grade, histological type and oestrogen receptor (ER) status.

RESULTS: Of 219 patients who had died with metastatic disease and who were under 70 years of age at metastatic presentation, 49 (22%) developed brain metastases. The development of brain metastases was related to young age (P = 0.0002), with 43% of women under 40 years developing brain metastases. Brain metastases were more common in women whose tumours were ER negative (38%) compared with women with ER-positive disease (14%) (P = 0.0003). By combining age and ER status, it is possible to identify a group of women (age under 50 years and ER negative) with a 53% risk of developing brain metastases. This group included many women who had chemotherapy for visceral metastases, and 68% had either stable disease or disease response at other sites at the time of brain metastases presentation.

CONCLUSION: It is possible to identify a subgroup of women with metastatic breast cancer at high risk of brain metastases who may benefit from pre-emptive medical intervention, such as screening or prophylactic treatment.

BACKGROUND: The occurrence of brain metastases is an emerging problem in patients with metastatic breast cancer. In the present study, we looked at risk factors for brain metastasis among patients with metastatic breast cancer.

PATIENTS AND METHODS: The risk factors for brain metastasis were first determined in a series of 215 patients with metastatic breast cancer. Risk factors identified in the multivariate analysis were re-evaluated in a confirmatory series of 199 patients with metastatic breast cancer. All the patients had been included in prospective randomized trials that evaluated chemotherapy or endocrine therapy in an adjuvant setting.

RESULTS: In the first series, the presence of lung metastases (hazard ratio = 4.3, 95% CI: 1.9-9.3, P=0.0003) and negative hormone receptor status (hazard ratio = 4.2, 95% CI: 1.7-11, P=0.002) were the only predictive factors associated with the occurrence of brain metastases in the multivariate analysis. The second series confirmed that the presence of lung metastases and negative hormone receptor status were associated with the occurrence of brain metastases.

CONCLUSION: The presence of lung metastases as the first site of relapse and a negative hormone receptor status are predictive for the occurrence of brain metastases in patients with metastatic breast cancer. A prophylactic treatment should be evaluated in these subsets of patients.

Adjuvant systemic treatment for breast cancer has evolved resulting in improved outcomes. A relevant question is whether these advances have changed the pattern of distant relapse. Women diagnosed with stage I-III breast cancer were divided into three time cohorts according to changes in adjuvant therapy; A: 1989-1991-CMF chemotherapy in premenopausal and tamoxifen for postmenopausal women; B: 1992-1997-anthracycline chemotherapy and tamoxifen for pre/postmenopausal women; C: 1998-2001-broader use of anthracyclines. The primary endpoint was 5-year cumulative incidence of bone metastasis (BM) as first site of metastasis (FSOM) versus non-bone metastasis (NBM). The ratios NBM/BM in each period were calculated. The eligibility criteria were met by 21,415 cases; Cohorts A: 1989-1991 (n = 3,915), B: 1992-1997 (n = 9,229) and C: 1998-2001 (n = 8,271). Between 1989 and 2001, the percentage of patients receiving adjuvant chemotherapy increased from 23.1 to 34.4%. A decline in cumulative 5-year incidence rates for BM and NBM as FSOM was seen comparing cohort A to C, P<0.0001. The ratio NBM/BM was significantly increased from 1.53 in the early cohort to 2.00 in the later one, P = 0.0083. The most prominent increase (84%) was in the ER-negative group, chemotherapy treated, P = 0.0272. A significant decline in 5-year cumulative incidence of metastases and an increase in the proportion of NBM as first site of metastasis were observed between earlier and later cohorts. This may reflect the need for more successful adjuvant treatment options for aggressive breast cancer subtypes which are more likely to present with early spread to visceral organs. Understanding patterns of relapse may help design new adjuvant strategies.