Pathologic analysis of tumor size and lymph node status in multifocal/multicentric breast carcinoma

BACKGROUND: For unifocal invasive breast carcinoma, increasing tumor diameter predictably correlates with a greater frequency of lymph node involvement, thereby facilitating treatment decisions. In invasive breast tumors presenting with multiple nodules, however, it is unclear whether tumor size correlates with lymph node dissemination in a similar manner. METHODS: The authors analyzed a series of 101 invasive breast carcinomas presenting with multiple macroscopically apparent lesions (2 foci: n = 77; 3: n = 20; 4: n = 4). Two different assessments of the tumor size (diameter of largest focus and combined diameter of all the foci) were then correlated with the status of axillary lymph nodes. For comparison with unifocal tumors, the authors used both external and internal control series (the latter consisting of 469 patients from their institution). The associations between lymph node status, tumor size, and multifocality were modeled using univariate and multivariate logistic regression, for each modality of tumor size assessment. RESULTS: The logistic curves for multifocal and unifocal tumors were significantly different when the largest diameter was used as a tumor size estimate. Multifocal cases had higher frequencies of lymph node involvement than unifocal lesions of similar size category. In a multivariate logistic regression, the odds ratio of positive lymph node status in multifocal versus unifocal cases was 2.8 using largest diameter as a tumor size estimate (P < 0.0001). When the combined diameter assessment was used, however, the regression curve of multifocal cases was similar to that of unifocal cases, and the frequency of lymph node positivity was not significantly different in multifocal versus unifocal cases of the same size (odds ratio, 1.4; P = 0.13). CONCLUSIONS: The authors' results show that, if aggregate diameters are used, unifocal and multifocal breast carcinomas are similar with respect to frequency of regional lymph node metastasis. Currently used algorithms, which use the diameter of the largest nodule, result in understaging of multifocal breast carcinomas due to underestimation of actual tumor size.     

Multifocal breast cancer documented in large‐format histology sections

BACKGROUND:

The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail.

METHODS:

In total, 444 consecutive invasive breast cancers that were documented in large‐format histology slides and worked up with detailed radiologic‐pathologic correlation were sampled into tissue microarray blocks and stained immunohistochemically to delineate the molecular subtypes.

RESULTS:

Diffuse or multifocal distribution of the invasive component of breast carcinomas in this series was associated with a 4.14‐fold respectively 2.75‐fold risk of cancer‐related death compared with unifocal tumors irrespective of molecular phenotype. Patients who had human epidermal growth factor receptor 2 (HER2)‐positive cancers; estrogen receptor‐negative, progesterone receptor‐negative, and HER2‐negative (triple‐negative) cancers; or basal‐like cancers had a 2.18‐fold, 2.33‐fold, and 4.07‐fold risk of dying of disease, respectively, compared with patients who had luminal A carcinomas. Unifocal luminal A, HER2‐positive, and basal‐like cancers were associated with significantly better long‐term survival outcomes than their multifocal or diffuse counterparts; luminal B and triple‐negative tumors also had the same tendency. In multivariate analysis, patient age, tumor size category, lymph node status, lesion distribution, and molecular phenotypes remained significant.

CONCLUSIONS:

Multifocality and diffuse distribution of the invasive component were associated with significantly poorer survival in women with breast carcinomas compared with unifocal disease in patients with luminal A, HER2 type, and basal‐like cancers. Molecular classification of breast cancer is a powerful tool but gains in power when combined with conventional and subgross morphologic parameters. Cancer 2013. © 2013 American Cancer Society.     

Early and more advanced unifocal and multifocal breast carcinomas and their molecular phenotypes

Background

I examined the relationship between the recently established prognostic parameter, molecular tumor phenotype and tumor size, lesion distribution (unifocal, multifocal, diffuse growth), and lymph node status.

Materials and Methods

I analyzed 660 consecutive invasive breast carcinomas documented in large-format histology sections. Immunohistochemistry was used to phenotype the tumors on the basis of estrogen and progesterone receptor expression, HER2 (human epithelial growth factor receptor 2) overexpression, and expression of basal markers.

Results

The proportion of luminal A tumors (84.8% vs. 71.6%; P < .0001) and basal-like tumors (5.0% vs. 14.8%; P < .0001) were significantly different in early (<15 mm) and more advanced invasive breast carcinomas, whereas the proportion of luminal B and HER2 type tumors (4.2% vs. 7.8%, and 5.7% vs. 4.8%, respectively) were not. All the phenotypes had similar percentages of multifocal tumors, whereas most diffuse invasive carcinomas were luminal A type. Early luminal A carcinomas had significantly fewer lymph node metastases (LNM) than more advanced carcinomas but luminal B and HER2 type tumors showed no such difference. This difference was evident (15.4% vs. 42.4%) but statistically not significant in the basal-like category. Multifocal tumors of all phenotypes had significantly higher frequencies of LNM compared with unifocal tumors.

Conclusion

Multifocality of the invasive component represents a negative prognostic parameter associated with significantly increased LNM in all phenotype, whereas larger tumor size was such a parameter only in the luminal A category. HER2 overexpression occurs early in the natural history of tumors and is associated with high LNM rates.     

Clinicopathological Characteristics of Primary Breast Cancer in Older Geriatric Women: A Study of 39 Japanese Patients over 80 Years Old

The number of primary breast cancers occurring in elderly women is increasing in Japan. Optimization of treatment regimens in this age group requires precise evaluation of the biological aggressiveness of these tumors as well as the performance status and extent of tumor spread. In 39 breast cancer patients who were at least 80 years old, we examined several parameters; the form of surgical therapy, the lymph node status, presence or absence of distant metastases, the histological type and grade of atypia, and overexpression of the c-erbB-2 oncoprotein in the cancer cells. They were correlated with the clinical outcome of the patient. Of the 33 patients who underwent a mastectomy and axillary lymph node dissection, five died from cancer recurrence. Only one out of 22 patients without lymph node metastases died from cancer, while four out of the eight patients with metastases to three or more lymph nodes died from cancer recurrence within 2.7 years of surgery. The overall survival curves also differed between patients with low-risk histological tumors or grade 1 or 2 invasive ductal carcinoma and those with grade 3 invasive dnctal/lobular carcinoma. Overexpression of c-erbB-2 also affected survival. Regional recurrence occurred in three out of the six patients for whom only lumpectomy or simple mastectomy was performed. These results indicate that, although primary breast cancer occurring in patients over 80 years old was largely of low-grade malignancy, patients with three or more lymph node metastases, invasive ductal/lobular carcinomas of grade 3, or c-erbB-2 overexpression frequently exhibited an aggressive clinical course.     

Expression of glycodelin protein and mRNA in human ductal breast cancer carcinoma in situ, invasive ductal carcinomas, their lymph node and distant metastases, and ductal carcinomas with recurrence

Glycodelin, previously known as PP14, has been localized in endometrial, ovarian and cervical carcinoma cells. Recently, glycodelin was demonstrated to be expressed in cancerous human breast tissue. In this study, paraffin-embedded slides of carcinoma in situ, invasive carcinomas without metastases, invasive carcinomas with corresponding lymph node metastases, invasive carcinomas with corresponding recurrence and invasive carcinomas with corresponding distant metastases were investigated for glycodelin protein and mRNA expression. Protein expression was found in all cases of carcinoma in situ, in invasive carcinoma without lymph node metastases in 90% of cases, in breast cancer with lymph node metastases in 50% of cases, in breast cancer with recurrence in 38% of cases and in breast cancer with distant metastases in 40% of cases. Results were confirmed by in situ hybridization showing reduced glycodelin expression as lymph node metastasis progressed, compared to carcinoma in situ. Glycodelin mRNA expression is not further reduced in carcinomas with distant metastasis and recurrence compared to carcinoma in situ. Results demonstrate that invasive breast carcinomas without metastases are more likely to express glycodelin. In contrast, cases of breast cancer with metastatic infiltration and recurrence show weak expression of glycodelin. On the basis of these results, we speculate that glycodelin could be used as a prognostic marker for breast cancer.     

Carcinoma in situ of the breast.

A series of 87 cases of carcinoma in situ of the breast was reviewed. IN 49 CASes in which lobular carcinoma in situ was shown on biopsy, three patients were found to have invasive carcinoma in the subsequently done mastectomy. All three of these cases were in a group of 14 patients shown in have bilateral lobular carcinoma in situ on biopsy. In a group of 38 patients with intraductal carcinoma on biopsy, seven were found to have invasive carcinoma in the mastectomy that was subsequently done. Lymph node metastases were found in one patient in the lobular group and four patients in the intraductal group. Three patients in the intraductal group died of cancer. None in the lobular group has died of cancer.     

Multifocal and multicentric breast cancer: does each focus matter?

PURPOSE: The identification of multiple tumors in the breast is associated with increased nodal involvement when compared with similar staged unifocal disease. This study compares two methods of tumor size assessment to predict tumor behavior in the relationship between size and axillary node involvement for patients with multifocal and multicentric breast cancer. METHODS: The histologic reports of every patient with multifocal breast cancer treated in New South Wales between April 1995 and September 1995 were examined. Tumors were assessed using two size estimates: (1) largest tumor focus diameter and (2) the aggregate diameters of all tumor foci. The dimensions were compared with unifocal tumors and against node positivity. RESULTS: Ninety-four (11.1%) of 848 women had multifocal breast cancer and of these 49 women (52.1%) had axillary node involvement compared with 37.5% with unifocal breast cancer (P =.007). The use of aggregate dimension reclassified significant numbers of multifocal tumors at a more advanced stage. Use of this method to stage cancers, rather than the largest tumor size, removed the excess node positivity when compared with unifocal, stage-matched breast carcinomas. CONCLUSION: The tendency of breast tumors to metastasize is a reflection of the total tumor load. Failure to measure the additional tumor burden provided by multiple small foci may understage a woman's disease. This may deny patients the opportunity of adjuvant therapies if the contribution of the smaller foci to the incidence of node positivity and survival is ignored.     

On the occurrence of focal, occult in situ and invasive carcinoma in 250 mastectomy specimens

In 1982, a total of 250 breasts were removed for cancer in the surgical departments of the Oslo City Health Department, comprising 81% of all new breast cancers reported in Oslo in 1982. Invasive ductal carcinoma (68%) and invasive lobular carcinoma (12.4%) were the predominant types. Special attention was given to the presence of occult in situ or invasive carcinomas more than 1 cm from the periphery of the main carcinoma. In 24.8% of the specimens, carcinoma in situ was found in such locations, and an additional 6.9% showed a second, occult invasive carcinoma. Carcinoma in situ was equally common in invasive ductal and invasive lobular carcinoma. Occult invasive carcinoma was predominantly found in specimens with invasive lobular carcinoma. There was a significantly increased number of lymph node metastases in patients with carcinoma in situ or second, occult primary carcinoma more than 1 cm from the periphery of the main carcinoma.     

Staging and treatment of clinically occult breast cancer

Five hundred fifty-seven biopsies were performed for clinically occult mammary lesions, detected by mammography as clustered calcifications or nonpalpable masses within the breast. One hundred seventy-five cancers were demonstrated within this group, including 106 invasive carcinomas, 10 microinvasive carcinomas, 45 in situ ductal carcinomas, and 14 lobular carcinomas in situ (lobular neoplasia). No patient with in situ or microinvasive carcinoma had evidence of axillary node metastases in 33 specimens studied. However, a disturbingly high proportion of those patients with invasive carcinomas, approximately 35%, had histologically confirmed axillary node metastases, despite the small size of the primary tumors. These observations suggest that the use of the term "minimal" cancer is misleading when applied to invasive carcinoma. Staging systems for breast cancer have been imprecise when referring to nonpalpable lesions. Cancers detected as clustered calcifications only or as areas of parenchymal distortion without an accompanying mass are properly considered as T-0 cancers, with a suggested T-0(m) to indicate that the lesion was detected by mammography. However, when the mammogram indicates the presence of a mass that proves to be malignant, although the clinical examination may have been negative, the cancer should be staged according to the size of the mass on the mammogram, with the notation that it was detected by mammography, e.g., T-1(m), T-2(m), etc. The incidence of axillary node metastases even in these so-called occult cancers is significant, so that recommendations for treatment for any invasive cancer, regardless of its size, must take these observations into account. Similarly, the incidence of multifocal sites of cancer within the breast, even in the noninvasive cancers encountered, must be remembered when treatment is suggested.     

Nerve fibers infiltrate the tumor microenvironment and are associated with nerve growth factor production and lymph node invasion in breast cancer

Infiltration of the tumor microenvironment by nerve fibers is an understudied aspect of breast carcinogenesis. In this study, the presence of nerve fibers was investigated in a cohort of 369 primary breast cancers (ductal carcinomas in situ, invasive ductal and lobular carcinomas) by immunohistochemistry for the neuronal marker PGP9.5. Isolated nerve fibers (axons) were detected in 28% of invasive ductal carcinomas as compared to only 12% of invasive lobular carcinomas and 8% of ductal carcinomas in situ (p = 0.0003). In invasive breast cancers, the presence of nerve fibers was observed in 15% of lymph node negative tumors and 28% of lymph node positive tumors (p = 0.0031), indicating a relationship with the metastatic potential. In addition, there was an association between the presence of nerve fibers and the expression of nerve growth factor (NGF) in cancer cells (p = 0.0001). In vitro, breast cancer cells were able to induce neurite outgrowth in PC12 cells, and this neurotrophic activity was partially inhibited by anti‐NGF blocking antibodies. In conclusion, infiltration by nerve fibers is a feature of the tumor microenvironment that is associated with aggressiveness and involves NGF production by cancer cells. The potential participation of nerve fibers in breast cancer progression needs to be further considered.     

Carcinoembryonic antigen immunoscintigraphy complements mammography in the diagnosis of breast carcinoma

BACKGROUND: An adjunctive noninvasive test that is predictable and highly specific for breast carcinoma would complement the high false-positive rate of mammography in certain patients. METHODS: This prospective, multicenter study evaluated the accuracy, safety, and immunogenicity of carcinoembryonic antigen (CEA) antibody imaging in women with known or suspected breast carcinoma. Scintigraphic breast images were obtained approximately 3-8 hours after the administration of technetium 99m ((99)Tc) labeled anti-CEA Fab' and correlated with histopathology. RESULTS: The (99)Tc labeled anti-CEA Fab' detected tumor CEA expression in 46 of 49 women (94%) initially entered with known primary breast carcinoma regardless of histology or serum CEA levels. In women scheduled for biopsy confirmation of mammographic and physical examination findings, 104 (99)Tc labeled anti-CEA Fab' studies had a sensitivity of 61% (17 of 28 cases) and a specificity of 91% (69 of 76 cases). In total, (99)Tc labeled anti-CEA Fab' detected 52 of 62 invasive ductal carcinomas, 5 of 5 invasive lobular carcinomas, and 3 of 6 noninvasive tumors (2 ductal carcinomas in situ and 1 intracystic papillary carcinoma). Tumor size significantly affected sensitivity (P = 0.041), with 11 of 14 missed lesions 相似文献   

Expression of c-erbB3 protein in primary breast carcinomas.

Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.     

The pathological findings of breast cancer in patients surviving 25 years after radical mastectomy

The authors report the findings in 107 women who are known to have survived 25 years from among a population of 746 consecutive patients who underwent radical mastectomy for breast carcinoma at the University of Chicago Hospitals and Clinics from 1929 to 1955. Of these patients, 103 had invasive carcinomas, two had intraductal carcinomas, and two had subareolar papillomatosis. Six patients had to be excluded because of inadequate pathologic material. The pathologic findings in 93 cases were compared with those in an equal number of control cases dying within a comparatively short period (median, 3.4 years; range 0.9-9.9 years) after radical mastectomy. These were matched for age, tumor size, and number of positive nodes. Only two of our patients suffered recurrences, and none died of her original tumor; however, 12 developed second primaries in the opposite breast, and four died from them. Compared with all patients who underwent radical mastectomy in this period, the 25-year survivors were younger (69 versus 43% were younger than age 50 years), had smaller tumors (39 versus 26% less than 2 cm in diameter), and a larger number (60 versus 39%) had negative nodes. Nonetheless, 12% of the survivors had tumors larger than 5 cm in diameter and 11% had four or more positive nodes. Histologically, 19% of the 25-year survivors had medullary, mucoid, infiltrating lobular, tubular or lipid rich carcinomas, whereas there was only one lobular and one apocrine carcinoma in the control group. Compared with controls, the survivors had a higher percentage of Grade I tumors and a lower incidence of lymphatic and vascular invasion in the breast. Only one 25-year survivor compared with 16 controls had blood vessel invasion. A surprising 63% of the 25-year survivors had lymphatic or vascular invasion within the tumor, or lymph node metastases compared with 82% of controls. While our studies confirm the importance of these well-known prognostic indicators, it also shows that some patients with pathologically unfavorable lesions, i.e., large tumors of high grade with extensive lymphatic invasion and many positive nodes, treated by radical mastectomy may survive for 25 years. However, we could not accurately predict, among the cases we studied, who would be expected to survive 25 years or who would die within four years.     

Radiological–Pathological Correlation in Diagnosing Breast Carcinoma: The Role of Pathology in the Multimodality Era

Breast carcinoma is a lobar disease, as the simultaneously or asynchronously appearing often multiple tumor foci originate from a single sick breast lobe. In its initial phase, the spatial pattern of malignant transformation may be lobar (targeting the entire lobe), segmental (targeting a segment) or terminal (targeting distant terminal ductal-lobular units) within the sick lobe. All these variations are properly characterized by the following parameters: the extent of the disease (the volume of the tissue containing all the actually present malignant structures within the breast), the distribution of the lesions within this tissue (unifocal, multifocal or diffuse, separately for in situ and invasive component), the size of the tumor (corresponding to the largest diameter of the largest invasive focus) and the exact localization of the lesion(s). In addition, intra- and intertumoral heterogeneity have to be noticed, if evident. Combining the results of different imaging modalities (mammography, ultrasound, magnetic resonance imaging) the radiologist may compensate the limitations of individual methods. This multimodality approach leads to more accurate radiological size measurement, more accurate assessment of the distribution of the lesions and disease extent. This represents a challenge for pathologists as the traditional histopathology method based on fragmentation and sampling of macroscopically suspicious lesion(s) is clearly insufficient for modern postoperative radiological-pathological correlation. There is a clear need for more complete examination of the excised tissue and for a three-dimensional reconstruction of the finding, preferably using continuous large tissue slices and two and three-dimensional large-format histological sections. Discordant results may still appear as a consequence of failure in radiological-pathological correlation or related to certain tumor subtypes as invasive lobular carcinoma of diffuse type, low grade in situ lesions or micropapillary ductal in situ carcinoma.     

Carcinome lobulaire à cellules pléomorphes du sein. Difficultés diagnostiques: à propos d’un cas avec revue de la littérature

We report a case of a 27-years-old woman with a lesion at the right breast, incidentally noted. The patient underwent tumour resection followed by a right mastectomy type “Patey”. Microscopic analysis of the tumour had recognised an invasive pleomorphic lobular carcinoma. Invasive pleomorphic lobular carcinoma (PLC) is a distinctive aggressive subtype of invasive lobular carcinomas (ILC). It has the typical infiltrating pattern of classical ILC of diffuse single cell spread but the nuclei aremore pleomorphic. Histological differential diagnosis with ductal carcinoma may be difficult, but it is important for this difference to be done. E-cadherine is a trans-membrane glycoprotein, typically expressed in ductal carcinoma, and loss of E-cadherine expression characterises invasive and in situ lobular carcinoma.     

The expression of Fhit protein is related inversely to disease progression in patients with breast carcinoma

BACKGROUND: The FHIT gene, located at human chromosome 3p14.2, frequently is deleted in a number of human tumors, including breast carcinoma. Its protein product (Fhit) is presumed to have tumor suppressor function. Loss of expression of a tumor suppressor gene is an important step in tumor progression from premalignant, to in situ, to invasive carcinoma. METHODS: In the current study, Fhit expression was examined in invasive carcinomas and in epithelial lesions representing stages of carcinoma progression in 50 mastectomy specimens using immunohistochemical methods. RESULTS: Normal ductal and lobular epithelium consistently and strongly expressed Fhit. A complete loss of or a significant reduction in Fhit expression was observed in 72% of breast carcinomas. A statistically significant, negative correlation in Fhit expression among the stages of disease progression in Fhit negative breast carcinomas was observed (normal epithelium > hyperplasia > atypical hyperplasia and carcinoma in situ > invasive carcinoma), whereas no loss of Fhit expression in precursor lesions was observed in Fhit positive tumors. CONCLUSIONS: These observations are consistent with the observed role of FHIT as a tumor suppressor gene in the pathogenesis of specific subsets of carcinomas.     

Subareolar injection of 99m-Tc sulfur colloid for sentinel nodes identification in multifocal invasive breast cancer

The objective were to study the relevance of the subareolar injection for sentinel node [SN] detection in multiple foci breast cancer. Seventy-nine patients with infiltrative breast carcinoma (diagnosed pre-operatively by core biopsy) and a mean age of 55 (31-78) years were enrolled. All patients were free of previous homolateral surgery, chemotherapy, locoregional radiotherapy or prevalent axillary lymph node. Using four 0.1 ml injections of 1.8 MBq, the technetium-99m 100 nm filtered sulfur colloid was injected by subareolar way (group I) in 16 cases of radiologically cancer with multiple invasive foci and 31 cases of radiologically unifocal cancer, and by peritumoral way (group II) in 32 cases of radiologically unifocal cancer. Scintigrams were obtained 2 to 4 hours after the injections and radioactive nodes were detected peroperatively 18 hours after the injection by intraoperative detection probe. Individual removal of all radioactive nodes was followed by axillary dissection at levels I and II of Berg including Rotter area control. All sentinel nodes were submitted to standard histopathological analysis on serial sections at 500 mu intervals completed by immunohistochemistry for cytokeratin on negative SN. SN were detected by scintigrams in 85% and 88% of the cases of group I and group II respectively, but in 98% and 97% of the cases of respectively both groups by intraoperative probe. Group I was composed of 69% ductal, 22% lobular and 9% tubular carcinomas, and group II of 87% ductal, 10% lobular and 3% tubular carcinomas. Seven and 5 radiologically unifocal tumors were in fact with multiple invasive foci at histology in groups I and II respectively. The complete scintigraphic procedure permitted the detection of a mean number of 2.7 (1-7) SN in group I and 2.3 (1-4) in group II (NS). In group I, the SN were metastatic in 22 patients (48%), 15 of them with the metastases being restricted to the SN, whereas in group II, the SN were metastatic in 9 patients (28%), 5 of them with the positivity restricted to the SN. No false negative result (SN negative and other axillary nodes positive) was observed in group I and only one false negative result in group II which was related to a cancer with histological multiple invasive foci. Sensitivities were 100% and 90%, and negative predictive values were 100% and 95%, for groups I and II respectively. Subareolar injection of radiocolloid allows identification of SN in cases of unifocal and multiple cancer. The mean number of SN detected by the subareolar method is not significantly different, although higher, to that detected by peritumoral injection.     

Correlation of tumor volume and surface area with lymph node status in patients with multifocal/multicentric breast carcinoma

BACKGROUND: Multicentric breast carcinomas have a higher frequency of axillary lymph node metastasis than unifocal tumors of similar stage. It remains unclear whether this merely reflects larger tumor volumes or a different biologic behavior. The authors have shown previously that when aggregate tumor diameter are used for staging, unifocal and multifocal tumors have a similar frequency of axillary lymph node metastasis. However, summing diameter overestimates actual tumor volume because volume is proportional to the third power of the diameter. Therefore, the aim of the current study was to reanalyze the relation between size and axillary lymph node status by correcting for tumor volumes and surface areas. METHODS: Volumes and surface areas of 122 breast tumor specimens with multiple macroscopic nodules (two foci: n = 95; three foci: n = 22; three foci: n = 5) were calculated by approximating the shape of each tumor nodule to an ellipsoid (for volume) or to a prolate spheroid (for area). For comparison, the authors used an internal control series, comprised of 469 macroscopic unifocal tumors. For all patients, multiple assessments of largest tumor size and combined size of all foci were correlated with the status of axillary lymph nodes. The associations between lymph node status, tumor volume or area, and multifocality were modeled using univariate and multivariate logistic regression. RESULTS: When either the largest or the aggregate tumor volume was used as a size estimate, tumor specimens with multiple nodules had a higher frequency of lymph node involvement compared with unifocal tumors of a similar volume or area. The odds ratio (OR) for having positive lymph nodes was 2.34 for aggregate volume measurement (P < 0.001). Surface area estimates yielded similar results (OR = 2.2, P < 0.001). CONCLUSIONS: Breast tumors with multiple macroscopic nodules had a different biology, with a propensity to dissemination at smaller tumor volumes (i.e., there was another factor besides volume alone that accounted for the differences in behavior).     

Ductal carcinoma in situ: value of sentinel lymph node biopsy

BACKGROUND: Ductal carcinoma in situ (DCIS) represents about 20% of newly diagnosed breast carcinomas. Axillary metastasis is often related to undiagnosed DCIS with microinvasion (DCISM). The aim of this study was to confirm the interest of sentinel lymph node (SLN) biopsy in extensive DCIS. METHODS: Patients with a diagnosis of DCIS or DCISM and axillary lymph node evaluation were selected. Surgical treatment included SLN biopsy and/or axillary lymph node dissection (ALND). Serial sections were stained with hematoxylin and eosin (H&E) and with an immunohistochemical (IHC) method. When a micrometastasis was found, the breast specimen was revised searching for occult microinvasion. RESULTS: Hundred and forty patients with initial DCIS were enrolled in the study. Node metastasis was identified in 9 patients (7%) of the 128 patients with DCIS and DCISM. At final histology, 4 (10%) of the 39 patients with pure DCIS and SLN biopsy and 1 (7%) of the 14 patients with DCISM and SLN biopsy had axillary micrometastasis. Four of the 12 patients upstaged to invasive carcinoma had metastatic SLNs. CONCLUSIONS: Sentinel lymph node biopsy is valuable in patients with diffuse DCIS or DCISM who are scheduled for mastectomy in order to search for axillary micrometastases and occult breast microinvasion.     

Sentinel node biopsy in patients with multiple breast cancer

BACKGROUND: Multicentric or multifocal breast cancer is considered a limitation for sentinel lymph node biopsy (SLNB). Studies showing that all quadrants of the breast drain via common afferent lymphatic channels indicate that multiple tumors do not affect lymphatic drainage. We therefore assessed the accuracy of SLNB in patients with multiple breast tumors. METHODS: Of the 942 breast cancer patients who underwent SLNB using radioisotope at Asan Medical Center between January 2003 and December 2006, 803 had unifocal and 139 had multiple tumors. Axillary dissection after SLNB was performed on 884 patients, 757 with unifocal and 127 with multiple tumors. All patients underwent lymphatic scintigram for removal of sentinel lymph nodes (SLNs). The clinical characteristics and accuracy of SLNB was compared in patients with unifocal and multiple breast cancer. RESULTS: In the multiple tumor group, 2.68 +/- 0.84 SLNs were identified in 136 of 139 patients (identification rate, 97.84%); 81.5% of SLNs were identified by scintigram. The incidence of axillary metastases was 29.50% (41/139). SLNB accuracy was 97.63% (124/127), with a false negative (FN) rate of 7.89% (3/38). In the unifocal group, 2.67 +/- 0.96 SLNs were identified in 787 of 803 patients (identification rate, 98.00%); 84.8% of SLNs were identified by scintigram. The incidence of axillary metastasis was 22.04% (177/803). SLNB accuracy was 98.02% (742/757), with a FN rate of 8.62% (15/174). The accuracy and FN rate of SLNB did not differ significantly between unifocal and multiple breast cancer. CONCLUSION: The accuracy of SLNB in multiple breast cancer is comparable to its accuracy in unifocal cancer. These findings indicate that SLNB can be used an as alternative to complete axillary lymph node dissection in patients with multiple breast tumors.