Multicentric Breast Carcinoma Research Articles

Concordance Between 21-Gene Recurrence Scores in Multifocal or Multicentric Breast Carcinomas Differs by Age and Histologic Subtype.

Among patients with multifocal or multicentric (MF/MC) breast cancer (BC) of similar morphology, concordance in Oncotype DX recurrence scores (RS) between tumors has been reported to be 87%. The effect of age and variation in histologic subtypes on RS concordance according to TAILORx criteria is unknown. We identified patients with MF/MC, estrogen receptor-positive, HER2-negative, node-negative BC with two or more RS results treated at our institution from 2009 to 2018. Patients were analyzed by age group (≤ 50 and > 50years). Low- and high-risk cut-offs were RS ≤ 25 and > 25 for age > 50years, and RS ≤ 20 and > 20 for age ≤ 50years. RS concordance was defined as no change in management based on RS variation between lesions. Overall, 120 patients with MF/MC BC were identified-82 (68.3%) aged > 50years and 38 (31.7%) aged ≤ 50years. Patients aged ≤ 50years had higher mean RS for both multifocal (20 vs. 14; p = 0.006) and multicentric (17 vs. 13; p = 0.003) tumors and more frequently had high-risk tumors (p < 0.0001). Among patients aged > 50years, 95.1% had RS concordance between tumors (same subtype, 98.2%; variable subtype, 88.9%; p = 0.1). Among patients aged ≤ 50years, RS concordance was 81.6%. Among patients with MF/MC BC, RS concordance was high, particularly in those aged > 50years with tumors of the same histologic subtype. RS testing of one focus may be sufficiently prognostic and predictive in patients aged > 50years, regardless of subtype concordance. Testing of individual foci should be considered in patients aged ≤ 50years due to a higher likelihood of RS discordance.

Integrating anatomy, radiology, pathology, and surgery: An alternative approach in resecting multifocal and multicentric breast carcinoma.

The sick lobe hypothesis provides the basis for a lobar approach in radiology, pathology, and surgical treatment of breast cancer. This approach aims to remove the tumor together with the surrounding field of genetic aberrations. Detailed preoperative lobar imaging that properly maps the disease and assesses its extent guides the parenchymal resection. Integration of our knowledge of breast anatomy and pathology with the results of preoperative radiological mapping is critical in assessing the eligibility of patients with multifocal and/or multicentric breast cancer for breast conservation treatment. Through an appropriately selected incision, a multisegment resection of the diseased lobe(s) is performed, which leaves the residual parenchyma in a formation that allows dovetailing of one part into the other, like the way pieces of a jigsaw puzzle fit together. Detailed pathologic analysis of the surgical specimen provides valuable feedback to the radiologist, establishes the completeness of surgical intervention, and generates predictive information for therapeutic decisions. Our approach is a step in continuous search for ideal tailored therapy to avoid under or over-treatment of breast cancer patients.

Multifocal and Multicentric Breast Carcinoma: A Significantly More Aggressive Tumor than Unifocal Breast Cancer.

There are still many questions that surround multifocal or multicentric breast carcinoma (MMBC). The aim of this study was to analyze the clinicopathological characteristics of MMBC and provide feasible suggestions for therapy. A total of 156 cases of MMBC in 3,597 invasive ductal breast carcinomas were collected and reviewed. Some factors related with prognosis such as tumor size, lymph node metastasis and others were assessed in each tumor focus, and mismatches among foci were recorded. The majority of MMBC had aggregate dimensions over 2 cm (85.90%). The rate of axillary lymph node metastasis was 56.41% (88/156) compared to unifocal tumors of 33.01% (1,136/3,441). Most cases had higher Ki-67 proliferative indices (91/156). Mismatches in ER status were present in 6 cases, PR in 4 cases, proliferative index (Ki-67) in 9 cases and HER2-positive status in 2 cases. The larger aggregate dimension of tumor, the higher metastatic rate of axillary lymph node and the high Ki-67 proliferative index seen in most cases, suggest that MMBC is biologically more aggressive than unifocal breast cancer. In addition, every focus should be tested owing to the existence of different expressions of immunostaining between foci.

A retrospective study on multifocal and multicentric vs. unifocal breast cancer. Preliminary results

Multifocal (MF) and multicentric (MC) breast cancers have been comprehensively studied, but they still remain a controversial subject for many senologists in regards to the best treatment options. Conservatory approach is reserved preponderantly to unifocal localization of the invasive breast carcinoma while in MF and MC the radically techniques are still the main option. The real impact of MC and MF breast cancers on survival is still unknown, but it is presumed to be worse. MF and MC breast cancers are currently over treated by radical mastectomy (RM). The AMAROS trial and also the Z0011 trial recently demonstrated that less surgery does not necessarily mean less local control or worse survival outcomes. About 450 women that underwent surgery for breast cancers stages I-III were included in this monocentric retrospective study; clinical and pathological data were obtained from the database of the Institute of Oncology ”Prof. Dr. Alexandru Trestioreanu” Bucharest. Our primary objective was to see if there is any difference in disease free survival in early breast cancer patients primary treated by conservative surgery according to unifocal (UF) vs. MF vs. MC feature of the invasive component. Our secondary objectives were to identify if there is any correlation between the conservative or radical type of surgery and other clinical and histologcal characterstics; if there is any differences in survival between UF vs. MF vs. MC breast carcinoma. Median follow-up was of 51 months. MC and MF cancers were present in 38 patients (8.4%) and 13 (2.9%) respectively and most of them were treated with mastectomy (6 MF and 19 MC) rather than with breast conservative surgery (BCS). In the entire data analyzed there was no statistical difference between event free survival (EFS) in the subgroup that underwent BCS vs. radical surgery (RS): 21 events (16.4%) vs. 53 events (16.61% ) (p=0.957), median EFS 99.79 mo 95% CI [92.67-106.91] mo vs. 98.19 95% CI [92.81-103.56] mo (p=0.773). We found a significant correlation between recurrence and a family history of cancer (p=0.035), the tumor/node/metastasis (p<0.001), type of surgery (p= 0.035). Relapse rate wasn’t significantly different whatever the type of surgery done. Median EFS wasn’t different between patients that underwent BCS and those that underwent RS. BCS is a reasonable option in selected UF/MC/MF cancers, particularly in younger women with small breast tumors.

Abstract P3-13-09: Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer

Abstract Introduction: Development of the nipple-sparing mastectomy (NSM) technique has constituted a significant advance in the surgical treatment of selected cases of breast cancer. The most important aspect of areolar complex preservation is the exclusion of carcinoma involving the nipple. The retroareolar surgical margin is usually sampled and subjected to an intraoperative evaluation by frozen section examination in order to avoid a second procedure. However, this method is not standardized resulting in variable rates of false-negative results. Here, a new technique is proposed for the intraoperative study of the retroareolar margin. This ex vivo study was conducted by performing a simulated NSM procedure for patients undergoing total mastectomy to assess the impact of these measures on the accuracy of retroareolar frozen section examination. Materials and Methods: Between September 2012 and April 2014, we studied 158 mastectomy specimens from patients undergoing total mastectomy for breast cancer at the Cancer Institute of the State of São Paulo. Inclusion criteria were stage Tis-T3 tumors, multifocal and multicentric breast carcinoma, unicentric carcinoma not suitable to quadrantectomy. Patients submitted to neoadjuvant chemotherapy were also included. To obtain the entire sample area, the terminal retroareolar milk duct bunch was isolated. Fragments approximately 1.5 cm in length were excised and sectioned in parallel at the base of the nipple using a cold bistoury. Three transverse histological sections (4 μm each) at 200 μm intervals that included the entire isolated fragments were subjected to frozen section examination. The sections were stained with hematoxylin-eosin (H&amp;E) and were evaluated. The remainder of each fragment was embedded in paraffin and 4 μm sections were subsequently stained with H&amp;E and examined. Results: A total of 158 mastectomy specimens involving mammary carcinoma of no special type were examined. These included 15 (9.5%) in situ stage tumors, 36 (22.8%) stage I tumors, 71 (44.9%) stage II tumors, and 36 (22.8%) stage IIIA tumors. Paraffin examinations identified 25 retroareolar fragments compromised by carcinoma, resulting in 16.1% prevalence. Of the frozen sections examined, 2/158 (1.3%) had false-negative results and 5/158 (3.1%) had false-positive results. For the former two cases, the corresponding paraffin examinations detected low-grade carcinoma in situ and a residual cell cluster with a diameter less than 1 mm. The latter was found in a mastectomy specimen from a patient that underwent neoadjuvant chemotherapy. For the three cases involving false-positive results, the corresponding paraffin examinations revealed no atypical ductal hyperplasia present, one sclerosing intraductal papilloma and one nipple syringomatous adenoma. Statistical analysis revealed that the frozen section examinations performed had a sensitivity rate of 92.0% and a specificity rate of 96.2%. In addition, the positive predictive value (PPV) was 82.1%, the negative predictive value (NPV) was 98.4%, and the accuracy was 95.4%. Conclusion: The frozen section examination technique described here detected nipple involvement in breast cancer with greater accuracy than the frozen section usually performed by most surgeons. Citation Format: Piato JR, Aguiar FN, Mota BS, Dória MT, Alves-Jales RD, Messias AP, Goncalves R, Mano MS, Soares JM, Ricci MD, Filassi JR, Baracat EC. Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-13-09.

Heterogeneity of Unilateral Multiple Breast Cancer: Implications for Biomarker Testing

OBJECTIVE:This study was to re-examine the usefulness of biomarker assays in all multiple tumors in the same breast, and to evaluate the genetic heterogeneity of unilateral multiple breast carcinoma.MATERIALS AND METHODS:All of the cases met the criteria for synchronous multicentric breast carcinomas. Tumors were either 5 cm apart or within the different breast quadrants, with no identifiable connection between lesions, and were diagnosed at the same time for an individual patient.RESULTS:In the present study, 32 tumors from 15 patients with synchronous unilateral breast cancer were immunostained for estrogen receptor (ER), progesterone receptor (PR), and HER-2, and also underwent microsatellite analysis using 10 polymorphic markers. The ER and PR expression profile was similar in all tumors from the same patient. Discordant HER-2 immunoreactivity was found and confirmed by HER-2 FISH test in one case, and heterogeneity in the microsatellite pattern was observed in 6 patients.CONCLUSION:With the routinely-used biomarkers (ER, PR, and HER-2), heterogeneity was minimal, however, with more frequent differences noted at the genetic levels.

Axillary Lymph Node Status and Prognosis in Multifocal and Multicentric Breast Carcinoma

According to tumor-node-metastasis classification, tumor size should be based only on the largest tumor for multifocal and multicentric (MFMC) carcinomas. We estimated tumor size of MFMC carcinoma using either largest dimension of the largest tumor (dominant tumor size) or sum of the largest dimension of all tumors (aggregate tumor size), and compared the risk of axillary lymph node metastasis and prognosis between MFMC and unifocal carcinoma. We retrospectively reviewed the file records of 3,616 patients with MFMC (258 patients, 7.1%) and unifocal (3,358 patients) carcinoma. In T1 and T2 tumor subgroups, using dominant (p = 0.001 and p < 0.001) and aggregate (p = 0.017 and p = 0.004) tumor size axilla-positivity ratio was significantly higher in MFMC carcinoma compared with unifocal carcinoma. In stage I and II disease classified according to either dominant or aggregate tumor size, there was no significant survival difference between MFMC and unifocal carcinoma patients. In patients with stage III disease by dominant and aggregate tumor size disease-free survival was significantly worse in MFMC carcinoma compared with unifocal carcinoma (p = 0.036 and p = 0.041); multifocality and multicentricity had no independent prognostic significance (p = 0.074 and p = 0.079). The risk of axillary metastasis in MFMC carcinoma was higher than unifocal carcinoma, regardless of the method employed for tumor size estimation. MFMC carcinoma staged according to either dominant or aggregate tumor size had similar survival with unifocal carcinoma. We recommend using the largest dimension of the largest tumor in estimation of tumor size for MFMC carcinoma.

Magnetic resonance imaging: value of diffusion-weighted imaging in differentiating benign from malignant breast lesions

Although magnetic resonance imaging (MRI) has a high sensitivity in the detection of tumours, there is still much discussion about its role in breast cancer detection. MRI is not yet routinely used to further characterize lesions in patients diagnosed with breast cancer. This study investigated the impact of preoperative MRI on the surgical treatment of women with biopsy proven breast cancer. The diagnostic value of preoperative MRI was compared with that of conventional imaging (mammography and ultrasonography), and the diffusion-weighted imaging technique was also evaluated. 40 women underwent conventional imaging and biopsy as part of the clinical workup. In addition, preoperative MRI was performed in each patient. The kinetics of contrast captation were monitored and apparent diffusion coefficients were calculated. All imaging findings were compared with the histopathologic results, which were used as the gold standard. Differences in tumour extent, as determined by ultrasonography, MRI and histopathology, were evaluated. Contrast captation kinetics curves are mostly aspecific, while apparent diffusion coefficient values seem to correlate much better with tumour malignancy. MRI correlated more accurately with histopathological findings than ultrasonography and even revealed unsuspected multifocal and multicentric breast carcinoma in 20 patients (50%). The surgical plan of seven patients (18%) was changed as a result of the additional information provided by MRI. Diffusion-weighted imaging as a complementary tool to contrast captation kinetics and morphologic measurements may increase the specificity of MRI and help in differentiating between benign and malignant breast lesions. In addition, MRI yields more precise information than mammography and ultrasonography about the exact location, the extent, the multifocality or multicentricity of the tumour and can also detect possible additional tumours. Although MRI will never replace mammography (screening) or ultrasonography as a test for breast cancer in women with no high risk (e.g. BRCA 1 or 2 carriers), its use in a preoperative setting may allow more accurate staging of the disease, which in turn could result in a change in the treatment planning.

Facteurs prédictifs et pronostiques des cancers du sein multifocaux

Objectives Multicentricity is not listed as a major prognostic parameter in invasive breast carcinoma, and is not by itself an indication of systemic adjuvant treatment. Furthermore, evaluating the size of these tumors is discussed. The aims of this study are to evaluate prognostic value of multicentricity, and to compare different way for measuring multicentric breast carcinomas. Patients and methods Between 2001 and 2008, 1458 patients having breast invasive carcinoma were included in Tenon Hospital, Paris, France; 16% had a multicentric cancer. We have compared impact of multicentricity on lymph node (LN) involvement, and compared 3 ways for measuring these cancers. Results LN involvement was significantly associated with multicentricity. We found an over-risk of 20% for LN involvement in patients having multicentric cancer, whatever the size of the tumors. Considering the diameter of the largest focus is the best way for measuring these cancers. Discussion and conclusion We did not find a subgroup of patients at low risk of LN involvement when having a multicentric breast cancers. These results lead us to extend indications of adjuvant chemotherapies in all multicentric breast cancer. These results should be validated by randomized prospective studies.

Paget’s disease is associated with eleven cancerous regions: a case report and therapeutic strategy

Paget's disease of the breast is an uncommon disorder that accounts for 1% to 3% of all mammary tumors. The incidence of underlying carcinoma associated with Paget's disease has been reported in 82% to 100% of cases. The finding of underlying carcinoma reaches almost 100% when a palpable lump is also present. In this rare case, we described a patient presenting with Paget's disease but no palpable lump. However, we found 11 independent regions which were all invasive ductal carcinoma after the operation. Considering this patient, we should pay more attention to a multifocal and multicentric breast carcinoma associated with Paget's disease. Furthermore, we believe the mammography examination and a modified radical mastectomy are the most appropriate treatments for this population in clinical practice.

Sensitivity of imaging for multifocal-multicentric breast carcinoma

BackgroundThis retrospective study aims to determine: 1) the sensitivity of preoperative mammography (Mx) and ultrasound (US), and re-reviewed Mx to detect multifocal multicentric breast carcinoma (MMBC), defined by pathology on surgical specimens, and 2) to analyze the characteristics of both detected and undetected foci on Mx and US.MethodsThree experienced breast radiologists re-reviewed, independently, digital mammography of 97 women with MMBC pathologically diagnosed on surgical specimens. The radiologists were informed of all neoplastic foci, and blinded to the original mammograms and US reports. With regards to Mx, they considered the breast density, number of foci, the Mx characteristics of the lesions and their BI-RADS classification. For US, they considered size of the lesions, BI-RADS classification and US pattern and lesion characteristics. According to the histological size, the lesions were classified as: index cancer, 2nd lesion, 3rd lesion, and 4th lesion. Any pathologically identified malignant foci not previously described in the original imaging reports, were defined as undetected or missed lesions. Sensitivity was calculated for Mx, US and re-reviewed Mx for detecting the presence of the index cancer as well as additional satellite lesions.ResultsPathological examination revealed 13 multifocal and 84 multicentric cancers with a total of 303 malignant foci (282 invasive and 21 non invasive). Original Mx and US reports had an overall sensitivity of 45.5% and 52.9%, respectively. Mx detected 83/97 index cancers with a sensitivity of 85.6%. The number of lesions undetected by original Mx was 165/303. The Mx pattern of breasts with undetected lesions were: fatty in 3 (1.8%); scattered fibroglandular density in 40 (24.3%), heterogeneously dense in 91 (55.1%) and dense in 31 (18.8%) cases. In breasts with an almost entirely fatty pattern, Mx sensitivity was 100%, while in fibroglandular or dense pattern it was reduced to 45.5%. Re-reviewed Mx detected only 3 additional lesions. The sensitivity of Mx was affected by the presence of dense breast tissue which obscured lesions or by an incorrect interpretation of suspicious findings.US detected 73/80 index cancers (sensitivity of 91.2%), US missed 117 malignant foci with a mean tumor diameter of 6.5 mm; the sensitivity was 52.9%Undetected lesions by US were those smallest in size and present in fatty breast or in the presence of microcalcifications without a visible mass.US sensitivity was affected by the presence of fatty tissue or by the extent of calcification.ConclusionMx missed MMBC malignant foci more often in dense or fibroglandular breasts. US missed small lesions in mainly fatty breasts or when there were only microcalcifications. The combined sensitivity of both techniques to assess MMBC was 58%. We suggest larger studies on multimodality imaging.

Clinicopathological feature and long-term prognosis of apocrine carcinoma of the breast in Japanese women

Because of the rarity of apocrine carcinoma and lack of standardized criteria for the diagnosis, the definitive conclusions of clinicopathologic features and the prognosis has not been determined. We retrospectively examined data on 2091 curatively treated Japanese patients with primary breast carcinoma. Among them, 33 (1.6%) who had been diagnosed of apocrine carcinoma were reviewed. Compared with non-apocrine carcinoma, apocrine carcinoma was characterized by less positive rates of ER and PR, and by frequent rates of unilateral multicentric breast carcinoma with significant difference. The clinicopathological factors influencing 12-year survival rate were lymph node metastasis, lymphatic involvement and vascular involvement. There was no difference in survival rates at 10 years after operation between apocrine carcinoma and non-apocrine carcinoma. Our result shows unique hormone response and unilateral multicentricity are only typical clinicopathological features of apocrine carcinoma.

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

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. 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. 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). 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).

Clinicopathologic features and incidence of invasive lobular carcinoma in Japanese women.

Intending to clarify the true incidence of invasive lobular carcinoma of the breast in Japanese women as well as the frequency of unilateral multicentricity, 362 cases of clinically defined monocentric breast cancer without pre-operative biopsy (previously fine needle aspiration or needle biopsy were routinely carried out for every case) were examined by whole mammary gland serial sectioning. On the basis of pathology and the World Health Organization classification of breast tumors, each case was assigned to one of two main histologic types: invasive lobular carcinoma (ILC) or invasive ductal carcinoma (IDC). Invasive lobular carcinoma was further separated into classic and variant types by employing previously published criteria. Twenty-one cases of ILC (5.8%) were diagnosed, which is more than in most previous Japanese studies. Unilateral multicentric breast carcinoma was detected in 9.5% of ILC and 16.1% of IDC (the difference was found not significant). Microscopically, ILC tumors were found to be, on average, larger than IDC. Patients with classic type ILC tended to be younger than those with variant type or IDC. Estrogen receptor expression was found more frequently in variant type ILC than in classic type. These results suggest that the incidence of invasive lobular carcinoma of the breast in Japanese women is low and that unilateral multicentricity is not significantly higher in ILC than in IDC.

Discrimination between multicentric and multifocal breast carcinoma by cytogenetic investigation of macroscopically distinct ipsilateral lesions

Discrimination between multicentric and multifocal breast carcinoma by cytogenetic investigation of macroscopically distinct ipsilateral lesions

Discrimination between multicentric and multifocal breast carcinoma by cytogenetic investigation of macroscopically distinct ipsilateral lesions.

Whether macroscopically distinct carcinomas in the same breast are clonally related (multifocal breast carcinoma) or unrelated (multicentric breast carcinoma) is no longer only a scientific-pathological issue but, because different therapeutic strategies may be preferable for cases with intramammary metastatic disease compared with cases of multiple primary breast carcinomas, one that may have profound clinical implications. We studied the evolutionary relationship among macroscopically distinct, ipsilateral breast carcinomas by cytogenetic analysis of 26 tumorous lesions from 12 patients. Sixteen of the 26 foci (62%) were found to contain clonal chromosome abnormalities. Two carcinoma foci were karyotypically abnormal in each of seven patients. Four of these cases had an evolutionarily related, cytogenetically abnormal clone in the two lesions from the same breast, whereas the remaining three cases had completely different clonal karyotypic aberrations in the separate foci. These results, together with our previous findings in five other informative cases, show that multiple, synchronous breast tumors sometimes arise through intramammary spreading of a single primary carcinoma, whereas on other occasions they are the result of the simultaneous emergence of pathogenetically independent carcinomas within the breast. In the total material, an association was seen between the proximity of the foci and the likelihood of them being karyotypically related.

Multicentric Breast Carcinoma: Evaluation of Clinicopathological and Immunohistochemical Characteristics.

Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In 7(3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.

Patient selection for breast conservation therapy with magnification mammography

Breast-conserving therapy (BCT) is an appropriate treatment for women with breast carcinoma of limited extent. This study was undertaken to determine the ability of microfocal spot magnification mammography to identify women with multifocal or multicentric breast carcinoma who were unlikely to have all gross carcinoma removed with a limited breast resection. Two hundred sixty-three women with mammographically visible ductal carcinoma in situ and stage 1 and 2 carcinoma who were clinical candidates for BCT were evaluated with magnification mammography before undergoing definitive local therapy. Biopsy specimens of additional abnormalities thought to have a greater than 2% risk of malignancy were obtained. Forty-seven women had other abnormalities in the index breast requiring intervention, and 216 had only the primary tumor identified. Mean age, cancer presentation, disease stage, and histologic tumor type did not differ between groups. BCT was successful in 97.2% of women without mammographic abnormalities versus 38% of women with abnormalities (p = 0.001). Clinical characteristics did not differ between patients undergoing successful BCT and those requiring mastectomy. Synchronous contralateral carcinoma was identified in 2.4% of women at risk. Magnification mammography allows accurate preoperative identification of patients requiring mastectomy or quadrantectomy and should be performed before diagnostic biopsy is done.

Unilateral Multicentric Breast Carcinoma Studied by Whole Mammary Gland Serial Sectioning.

The incidence and clinicopathologic features of unilateral multicentric breast cancer (UMBC)were studied by mammary gland serial sectioning in 116 cases of clinically defined monocentric breast cancer (MONBC) examined histopathologically at the Nagano Cancer Detection Center. UMBC was defined as: 1) histopathologically discontinuous tumors each with an intraductal spread, 2)at least one tumor-free section separating two tumors, and 3) a large primary tumor and other small secondary tumors. UMBC was detected in 23 of 116 cases (19.8%), all with one secondary tumor. Primary and secondary tumors were located in the same quadrant in 34.8% and in different ones in 65.2%. The secondary tumors were < 5 mm in size in 56.5%. Secondary tumors, averaging 8.3 mm in size and 25.5 mm in distance from the primary tumor, were almost exlcusively noninvasive carcinomas, including 15 (65.4%) noninvasive ductal carcinomas and several special types. The primary and secondary tumors were of the same histologic type in 3 of 23 cases. UMBC patients averaged 6 years younger than MONBC patients, and the incidence of UMBC tended to be higher in younger patients (P<0.1). UMBC tended to occur more frequently in quadrant B with an average histologic tumor size significantly smaller than that in MONBC (P <0.01). The histologic types of the primary tumor in UMBC and MONBC were similar, with common types predominant. Lymph node metastases tended to be slightly more frequent in MONBC. This high incidence of UMBC calls for careful attention when considering breast conserving therapy.

Diagnosis of Breast Carcinoma with Radiolabeled Monoclonal Antibodies (MoAbs) to Carcinoembryonic Antigen (CEA) and Human Milk Fat Globulin (HMFG)

The current study attempted to assess the potential proficiency of radioimmunodetection (RAID) of primary, residual, multicentric, and recurrent breast carcinoma using two radiolabeled murine monoclonal antibodies (MoAbs), anti-human milk fat globulin (HMFG1) labeled with iodine (123I) and anti-carcinoembryonic antigen (CEA) labeled with technetium (99Tc). Thirteen patients with suspicious clinical and/or mammographic primary or recurrent breast carcinoma were studied in a phase I-II prospective, consecutive, nonrandomized, noncontrolled study. Five patients received intravenous infusion with 0.5-2.0 mg anti-CEA MoAb type CYT 380 labeled with 99Tc [13-22 millicurie (mCI)] and 8 patients received intravenous infusion with 0.25-1.0 mg anti-HMFG1 MoAb (Unipath, U.K.) labeled with 123I (4-17 mCI). Both MoAbs used in this study demonstrated ability to bind specifically to breast cancer lesions, resulting in successful RAID in 10 of 12 of studied patients (5 of 5 patients in the anti-CEA-99Tc and 5 of 7 in the anti-HMFG-123I group--accuracy 83.3%). One patient was excluded due to protocol violation. Seven patients had true-positive scans when correlated with surgery (sensitivity 87.5%). The MoAb scans accurately diagnosed lesions in 3 of the 4 primary invasive breast carcinomas confirmed histologically. Presence of residual carcinoma following wide excision was established in 1 of 2 patients and presence of soft tissue metastases in 3 patients. Three patients had true-negative scan (specificity 75%): 2 patients presented with suspicious mammographic recurrence postlumpectomy and 1 patient had questionable soft tissue recurrence. One patient with primary breast carcinoma had a false-negative scan and another had a false-positive scan in the presence of fibrosis following lumpectomy and radiation therapy. No adverse reactions were noted in the patients studied. RAID findings were confirmed by immunohistochemistry in 6 of 9 cases studied. Our data suggest that radiolabeled MoAbs used in this study are potentially useful diagnostic agents for evaluation of primary or recurrent breast carcinoma, particularly in the areas where conventional methodology is limited.