Influence of histology on the effectiveness of adjuvant chemotherapy in patients with hormone receptor positive invasive breast cancer.

INTRODUCTION: To investigate the effect of adjuvant chemotherapy on long term survival in addition to hormonal therapy in the systemic treatment of hormonal receptor positive breast cancer patients. METHODS: All patients with primary non-metastatic hormonal receptor positive invasive lobular (mixed) (=ILC) and invasive ductal (=IDC) breast cancer operated on between 1986 and 2007 were identified from a population based cohort. Four hundred ninety-eight patients with lobular (mixed) and sixteen hundred seventeen with ductal cancer were eligible. Both groups were divided in patients receiving adjuvant hormonal treatment with or without systemic chemotherapy. RESULTS: Overall survival was not statistically different in patients with ILC treated with adjuvant hormonal and chemotherapy compared to hormonal treatment alone (5-year survival 85.2% vs 82.8%, P = .68). In contrast, patients with IDC receiving adjuvant hormonal and chemotherapy had a significantly better overall survival compared to hormonal therapy alone (5-year survival rate 87.6% vs 80.8%, P < .001). In the multivariate analysis however, this significance disappeared suggesting that the data are possibly too small, too unbalanced, or influenced by other confounding factors to come to definitive conclusions. CONCLUSIONS: There are good reasons to consider ductal and lobular breast cancers as different entities in future studies. Patients with hormone receptor positive ILC seem to benefit differently from additional adjuvant chemotherapy to hormonal therapy as compared with patients with IDC.

The impact of postmastectomy radiotherapy on local control in patients with invasive lobular breast cancer.

PURPOSE: The aim of this population-based study was to examine the impact of postmastectomy radiotherapy on the risk of local recurrence in patients with invasive lobular breast cancer (ILC). METHODS: The population-based Eindhoven Cancer Registry was used to select all patients with ILC, who underwent mastectomy in five general hospitals in the southern part of the Netherlands between 1995 and 2002. Of the 499 patients 383 patients fulfilled the eligibility criteria. Of these patients, 170 (44.4%) had received postmastectomy radiotherapy. The median follow-up was 7.2 years. Fourteen patients (3.7%) were lost to follow-up. RESULTS: During follow-up 22 patients developed a local recurrence, of whom 4 had received postmastectomy radiotherapy. The 5-year actuarial risk of local recurrence was 2.1% for the patients with and 8.7% for the patients without postmastectomy radiotherapy. After adjustment for age at diagnosis, tumour stage and adjuvant systemic treatment, the patients who underwent postmastectomy radiotherapy were found to have a more than 3 times lower risk of local recurrence compared to the patients without (Hazard Ratio 0.30; 95% Confidence Interval: 0.10-0.89). CONCLUSION: Local control is excellent for patients with ILC who undergo postmastectomy radiotherapy and significantly better than for patients not receiving radiotherapy.

Uncommon breast tumors in perspective: incidence, treatment and survival in the Netherlands.

The relatively small group of patients with breast tumors other than the ductal, lobular or mixed ducto-lobular types, has reached nonnegligible numbers due to the ongoing increase in the incidence of breast cancer. We investigated stage and grade distribution of uncommon breast tumors using the nation-wide Netherlands Cancer Registry (population 16.5 million) and incidence patterns, treatment and long-term survival (up to 19 years) using the regional Eindhoven Cancer Registry (population 2.4 million). Incidence of all uncommon breast tumors together was 9.2/100,000 person years (age-standardized, ESR). The proportion of stage I tumors was 70% among patients with tubular (n = 3,456) and 40-50% for mucinous (n = 3,482), papillary (n = 1,078), cribriform (n = 503) and neuroendocrine (n = 76) tumors, contrasting to 27, 28 and 36%, respectively among patients with Signet ring cell cancer (n = 75), Paget's disease (n = 818) and the common invasive ductal carcinomas (n = 121,656). A better age-, stage-, and grade-adjusted prognosis was observed for patients with lobular (death risk ratio 0.8, 95%CI: 0.7-0.9), mucinous (0.5, 0.3-0.9), medullary (0.5, 0.3-0.9) and tubular (0.4, 0.2-0.6) carcinoma or phyllodes tumor (0.02, 0.0-0.2), compared with invasive ductal carcinomas. For patients with papillary (0.6, 0.2-1.6) and cribriform (0.1, 0.0-5.1) tumors better prognosis was not statistically significant. In conclusion, histologic type was an essential determinant of survival for about 10% of all newly diagnosed women with invasive breast cancer. Because patients with mucinous, tubular, medullary and phyllodes tumors have such a good prognosis, less aggressive treatment should be considered in some cases whereby specific guidelines are becoming increasingly desirable. Communication to patients with these specific histological types should reflect this.

Detection of HER2 amplification in breast carcinomas: comparison of Multiplex Ligation-dependent Probe Amplification (MLPA) and Fluorescence In Situ Hybridization (FISH) combined with automated spot counting.

In this study the detection of HER2 gene amplification was evaluated using Fluorescence In Situ Hybridization (FISH; PathVysion) in comparison with Multiplex Ligation-dependent Probe Amplification (MLPA), a PCR based technique. These two methods were evaluated on a series of 46 formalin fixed paraffin embedded breast carcinomas, previously tested for protein overexpression by HercepTest (grouped into Hercep 1+, 2+ and 3+). HER2 gene amplification (ratio > or =2.0) by FISH was found in 9/10, 10/30 and 0/6 in IHC 3+, 2+ and 1+/0 cases, respectively. Digitalized automated spot counting performed with recently developed CW4000 CytoFISH software was 100% concordant with manual FISH scoring. Using MLPA 18/46 samples showed a clear HER2 amplification. Comparing MLPA and IHC showed the same results as for FISH and IHC. All but one FISH positive cases (18/19) were confirmed by MLPA for the presence of the gene amplification. The overall concordance of detection of Her2 gene amplification by FISH and MLPA was 98% (45/46). Furthermore, both the level of amplification and equivocal results correlated well between both methods. In conclusion, MLPA is a reliable and reproducible technique and can be used as an either alternative or additional test to determine HER2 status in breast carcinomas.

Determinants of prognosis in breast cancer patients with tumor involvement of the skin (pT4b).

Determinants of prognosis were studied in patients with breast cancer with histologically proven tumor extension to the skin without clinical evidence of distant metastases (i.e., pT4b N0-3 M0). Data were collected retrospectively on 77 consecutive patients diagnosed in one community teaching hospital over the period from 1980 to 1995. The prognostic factor of tumor size showed a 5-year survival rate for patients with a tumor

Breast cancers found by screening: earlier detection, lower malignant potential or both?

A population-based study was performed to compare the characteristics of clinically detected breast cancers and cancers detected by the Dutch screening program. To determine whether differences are most likely to be explained by earlier diagnosis or by the detection of biologically different cancers in the screening program, comparisons were stratified according to tumor size. Data were obtained from the population-based Eindhoven Cancer Registry. During the period 1996-1999, 568 screen-detected and 630 clinically detected invasive breast cancers were available for analysis. Compared with patients with clinically detected breast cancer, women with screen-detected breast cancer had smaller tumors (P < 0.0001), were more likely to have negative lymph nodes (P < 0.0001), tumors with a positive estrogen (P = 0.007) or progesterone (P = 0.019) receptor status and a lower mitotic activity index (P = 0.009). In the group with cancers < or = 1.0 cm the screen-detected were more likely to have negative estrogen receptors (P = 0.027). The group with screen-detected tumors 1.1-2.0 cm across were more likely to have positive estrogen and progesterone receptors (P = 0.005 and P = 0.044, respectively) and tended to have a lower mitotic activity index (P = 0.078). No significant differences were found between screen-detected and clinically detected breast cancers of 2.1-3.0 cm across. After adjustments for tumor size, most of the differences between clinically detected and screen-detected breast cancers disappeared, suggesting that screen-detected breast cancers represent tumors in an earlier phase of their development, not a biologically different class.