Sakari Toikkanen

Invasive lobular carcinoma of the breast has better short- and long-term survival than invasive ductal carcinoma.

The outcome and prognostic factors of 217 women with invasive lobular carcinoma (ILC) and those of 1121 women with invasive ductal carcinoma (IDC) of the breast were compared. The patients were followed up for 10-43 years. Women with ILC had axillary nodal metastases less frequently than those with IDC (43% vs 53%, P = 0.02), although there was no difference in the primary tumour size between the groups. ILCs were more frequently of low grade, had lower mitotic counts and had less tumour necrosis. Furthermore, ILCs had lower S-phase fractions and were more often DNA diploid in flow cytometric analysis than IDCs (P < 0.0001 for all comparisons). The 5- and 30-year corrected survival rates of women with ILC were 78% and 50%, respectively, compared with 63% and 37% for women with IDC (P = 0.001). Small pT1NOMO ILCs (n = 41) had 100% 10-year and 83% 20-year corrected survival rates. In a multivariate analysis, a large primary tumour size, the presence of axillary nodal metastases, a high mitotic count and the presence of tumour necrosis all had an independent prognostic value in ILC. We conclude that ILC is associated with better survival than IDC.

The prognostic significance of nuclear DNA content in invasive breast cancer--a study with long-term follow-up.

The nuclear DNA content of 351 breast carcinomas was determined by flow cytometry from paraffin-embedded tissue to assess the prognostic significance of DNA ploidy, the DNA index (DI) and the S-phase fraction (SPF). The minimum follow-up of the patients was 22 years, and they were all from a defined urban population. DNA ploidy correlated with histological type and grade, mitotic count and nuclear pleomorphism (P less than 0.0001), and also with axillary nodal status (P = 0.0005), tumour necrosis (P = 0.001), primary tumour size (P = 0.03), menopausal status (P = 0.004) and the presence of distant metastases at the time of the diagnosis (P = 0.04). Survival corrected for intercurrent deaths of the patients with a diploid tumour was better than that of the patients with a non-diploid tumour (P = 0.0001, 48% vs 28% at 25 years). SPF had prognostic significance in both axillary node positive and negative patients, but ploidy and DI only in the node negative group, and their significance was greater in post-menopausal than in premenopausal patients. Axillary nodal status, primary tumour size, histological grade and the type of tumour margin circumscription were the most important independent prognostic factors in Coxs multivariate analysis, and SPF had independent prognostic value, whereas ploidy and DI did not. It is concluded that DNA ploidy, DI and SPF have long-term prognostic significance in breast cancer.

Pure and mixed mucinous carcinomas of the breast: A clinicopathologic analysis of 61 cases with long-term follow-up

Sixty-one mucinous carcinomas (MCs) of the female breast were followed-up for at least 18 years or until death (mean follow-up time, 26 years; median follow-up time, 23 years). The 61 MCs were compared with 441 unselected cases of breast carcinomas of all histologic types (reference carcinomas or RCs), which were follow-up for at least 21 years. When the MCs were divided into pure (PMCs) and mixed (MMCs) mucinous carcinomas, the 20-year cumulative corrected survival rate for operable cases in the PMC group was 79% +/- 11% (SE) and 28% +/- 13% for the MMC group. The difference is statistically significant (P less than .001). The PMCs had a significantly better survival rate (P less than .001) when compared with the RCs (20-year corrected survival rate, 41% +/- 3%). The survival rates for the MMCs and RCs did not differ significantly from each other. By Coxs multivariate analysis, pure histologic type and a tumor size less than 5cm were independent favorable prognostic factors in the MC group, but nodal status was closely related to the histologic type. Judging from the relative survival curves, no significant excess mortality of cancer occurred toward the end of the follow-up period in the PMC group.

Prostatic dysplasia associated with increased expression of C-MYC in neonatally estrogenized mice

Neonatal estrogenization of the mouse with diethylstilbestrol (DES; 2 micrograms./pup/day for days 1 to 3) or 17 beta-estradiol (200 micrograms./pup/day for days 1 to 3) resulted in epithelial dysplasia in the posterior periurethral region of the prostate at the age of 1 year. The dysplastic lesions ranged from mild to severe and, in addition to emergence of nuclear anaplasia, the architectural pattern of the glands was disturbed. Prenatal estrogenization (100 micrograms./kg. of maternal body weight on days 13 and 15 of gestation) only resulted in mild epithelial hyperplasia and occasional dysplasia in the ventral lobe of the prostate, but not in the posterior periurethral region. When neonatally estrogenized mice were allowed to grow until the age of 18 months, the degree and extent of the dysplasia of the posterior periurethral region was increased, but no frank invasion or metastases could be demonstrated. Combined estrogen and androgen treatment of neonatally estrogenized mice for 3 months (between 9 and 12 months of age) augmented nuclear dysplasia, but no invasive growth was seen in this group, either. Mild epithelial dysplasia was found in the dorsolateral lobes and coagulating glands of similarly treated control animals. A relation between the activation of certain proto-oncogenes and the development of several cancers has been shown in humans and experimental animals. In the present study, Northern blot analysis of total RNAs showed that the levels of c-myc mRNA were increased in the ventral and dorsolateral lobes, coagulating glands and prostatic urethra of neoDES mice at the age of 9 months. However, it remains to be determined whether the increase in c-myc expression is involved in the development of hyperplastic and dysplastic changes in the prostate of neoDES mice.

DNA index and S‐phase fraction and their combination as prognostic factors in operable ductal breast carcinoma

The prognostic significance of DNA ploidy, DNA index (DI), and S‐phase fraction (SPF) and their various combinations were studied together with 16 other clinicopathologic factors in 222 patients with operable invasive ductal breast carcinoma. The patients have been followed for a minimum of 22 years after the diagnosis or until death. Nuclear DNA content was determined by flow cytometry from paraffin‐embedded tissue. Patients with DNA diploid cancer (n = 57, 26%) had better survival rate corrected for intercurrent deaths than patients with nondiploid cancer (P = 0.002), and also, a small SPF (±14%, calculated in 134 cases) was associated with a favorable outcome in a univariate analysis (P = 0.01). The prognostic value of the DI and SPF was increased if they were combined. The most effective combination was obtained if diploid cancers were grouped together with DNA aneuploid cancers with a DI < 2.1 and an SPF < 14%. This combination had considerable prognostic value in a univariate analysis (P = 0.0002) and had independent prognostic value (P < 0.04) in Coxs multivariate analysis together with the primary tumor size (P < 0.001) in axillary node negative patients but not in axillary node positive patients. in the whole series the presence of axillary nodal metastases (P < 0.001), high mitotic count (P < 0.001), a large primary tumor size (P = 0.001), poorly circumscribed tumor margin (P = 0.005), and slight or absent tubule formation (P = 0.05) were the only independent prognostic factors in a multivariate analysis.

Mammography screening interval and the frequency of interval cancers in a population-based screening

In a population-based mammography screening, 129,731 examinations were carried out among 36,000 women aged 40-74 in the city of Turku, Finland, in the period 1987-94. Women older than 50 were screened at 2-year intervals, and those younger than 50 at either 1-year or 3-year intervals, depending on their year of birth. Screen-detected breast cancers numbered 385 and, during the same time period, 154 women were diagnosed with breast cancer outside screening in the same age group in the same city, and 100 interval cancers were detected. Two hundred and fifty (67%) of the screen-detected cancers were of post-surgical stage I compared with 45 (45%) of the interval cancers and 52 (34%) of the cancers found outside screening (P<0.0001). However, among women aged 40-49 the frequency of stage I cancers did not differ significantly among screen-detected cancers, interval cancers and cancers found outside screening (50%, 42% and 44% respectively; P=0.73). Invasive interval cancers were more frequent among women aged 40-49 if screening was done at either 1-year (27%) or 3-year intervals (39%) than in older women screened at 2-year intervals (18%; P=0.08 and P=0.0009 respectively). Even if adjusted for the primary tumour size, screen-detected cancers had smaller S-phase fractions than interval cancers or control cancers (P=0.01), but no difference in the S-phase fraction size was found between cancers of women younger than 50 and those older than this (P=0.13). We conclude that more interval cancers were found among women younger than 50 than among those older than 50 and that this could not be explained by the rate of cancer cell proliferation.

Glycogen-rich clear-cell carcinoma of the breast: A clinicopathologic and flow cytometric study

Six glycogen-rich clear-cell carcinomas (GCC) were found among 439 cases of breast cancer (BC) in a thorough search among a defined urban population. Five of these six patients had axillary lymph node metastases at diagnosis and all five died from their breast cancer within 7 years following the diagnosis. Tumors with histologic features of GCC were larger (P = 0.03), and they had a large DNA index (greater than 1.3) in flow cytometric DNA analysis more frequently than BCs in general (P = 0.04). All GCCs were nondiploid and had a high S-phase fraction (greater than 9%, mean 19.2%), which suggests that BCs with glycogen-rich cell features may be more aggressive than BCs in general.

Extensive squamous metaplasia simulating squamous cell carcinoma in benign breast papillomatosis.

An example of extensive squamous metaplasia simulating squamous cell carcinoma and arising in a case of benign breast papillomatosis is described, A benign breast lesion with squamous metaplasia as extensive as noted in this case has not been previously reported.

DNA aneuploidy in ectopic pregnancy and spontaneous abortions

The nuclear DNA content of 55 ectopic tubal pregnancies was studied by flow cytometry from paraffin embedded tissue blocks. An abnormal amount of DNA content was found in 24% of the cases. This was a significantly higher percentage than encountered in 92 spontaneous abortions studied by the same method in the same population (8%, P = 0.01). The result indicates that, in addition to the maternal factors, abnormal embryogenesis with grave chromosomal aberrations may play a major role in the etiology of ectopic pregnancy.

Long-term survival in node-positive breast cancer treated by locoregional therapy alone.

To investigate the long-term survival rate of node-positive (pN+) breast cancer treated by locoregional therapy alone, we made an attempt to identify all such patients followed up for at least 15 years after treatment in a defined geographical area (city of Turku, Southwestern Finland) and time period (1945-79) using the files of the local hospitals and the Finnish Cancer Registry. The clinical and autopsy records and histological slides of 1172 women diagnosed with breast cancer in the city were reviewed. From this cohort we identified 339 women with unilateral node-positive breast cancer treated with locoregional therapy without systemic adjuvant therapy. The relative survival rate of the cohort compared with the general female population matched for age and year of follow-up was calculated. The 15- and 30-year survival rates corrected for known intercurrent deaths were 26% (95% CI, 21-31%) and 21% (16-26%) respectively, and the relative survival rates 23% and 21% respectively. None of the patients with pN2 disease survived for 15 years, whereas the 30-year corrected survival rate in pN1 disease was 24% (18-30%). Women with pT1N1M0 cancer had as high as 59% (43-75%) 15-year survival rate corrected for intercurrent deaths. A trend for improving survival was found by the decade of diagnosis. The results indicate that a considerable proportion of women with pN1 breast carcinoma treated with locoregional therapy alone become 30-year survivors and are probably cured. Adequate locoregional treatment is mandatory in the care of node-positive breast cancer.