Breast cancer multifocality was studied in mastectomy specimens by correlated specimen radiography and histologic techniques. The patients chosen for study were comparable to those eligible for breast-conserving surgical therapy. Two study groups, one with 282 invasive cancers (T1-2) and the other with 32 intraductal cancers, were selected from a group of 399 consecutive cases by omitting patients who were clearly, or very probably, not candidates for breast-conserving surgical therapy according to current trial criteria. Omitted patients included those with clinically and/or radiologically multifocal cancers and patients with tumor extension into the chest wall or skin (7%). Also excluded were the so-called diffuse invasive cancers (8%), the clinically and radiologically occult tumors (3%), and the invasive cancers larger than 5 cm (3%). Of the 282 invasive cancers, 105 (37%) showed no tumor foci in the mastectomy specimen around the reference mass. In 56 (20%) tumor foci were present within 2 cm, and in 121 (43%) tumor was found more than 2 cm from the reference tumor. In 75 (27%) the tumor foci beyond 2 cm were histologically noninvasive cancers, and in 46 cases (16%) they contained invasive cancers as well. A comparison between the group with reference tumors less than 2 cm and the group with reference tumors more than 2 cm in size showed no significant difference between the groups in terms of presence or absence of tumor foci or distance of tumor foci from the reference tumor. If the 264 invasive cancers in this series that were 4 cm or less in diameter had been removed with a margin of 3 to 4 cm, 7% to 9% of the patients would have had invasive cancer left in the remaining breast tissue, and 4% to 9% would have had foci of noninvasive cancer left in the remaining breast tissue. On the basis of the data on the distribution of tumor at different distances from the reference tumor, the current study estimates the expected rates of local recurrences after breast-conserving surgical procedures relative to the extensiveness of the excision. The possible impact of postoperative local radiation therapy on the rates of expected local recurrence is discussed.

Histologic multifocality of Tis, T1-2 breast carcinomas. Implications for clinical trials of breast-conserving surgery.

Seventy-eight examples of intraductal carcinoma (DCIS) were identified after pathologic review of 2072 specimens obtained from National Surgical Adjuvant Breast Project protocol 6. This randomized clinical trial compares the therapeutic merit of total mastectomy (TM) with lumpectomy (L), with (LX) and without (LO) postoperative irradiation. All patients were subjected to axillary lymph node dissection. Seven (14%) of the 51 patients with DCIS treated by L exhibited breast recurrence within or close to the site of the initial lesion 4 to 53 months (average, 16 months) after L. Only 2 (7%) of these events occurred in the 29 women treated by LX, as opposed to 23% in the LO group. No pathologic features were noticed that might have been considered predictive of local breast recurrence. The three DCIS recurrences and the four invasive forms noted are considered to represent overlooked or incompletely excised foci of cancer because of the multifocality (not multicentricity) of some breast cancers. The possibility that DCIS may represent a marker of risk for the development of cancer rather than a precursor lesion per se is suggested. Despite apparent difficulties in the pathologic diagnosis of DCIS as well as uncertainty concerning its natural history, no evidence was found to indicate that it represents a more ominous disease than invasive cancer. Indeed, treatment failure occurred in only one patient treated by LX and a similar number subjected to TM (4% versus 2%). Although these observations are short term (average follow-up, 39 months), estimates of the probability of local recurrence or survival suggest that they will not be significantly altered after longer periods of surveillance. Thus, there are no compelling reasons why DCIS may not be treated in a cosmetically acceptable manner by LX. A randomized clinical trial addressing this issue is now in progress.

Pathologic findings from the National Surgical Adjuvant Breast Project (protocol 6). I. Intraductal carcinoma (DCIS).

Twenty-eight women with ductal carcinoma in situ (DCIS) of the breast treated by biopsy only were identified in a histologic review of 11,760 biopsies performed between 1950 and 1968. Seven of the 25 women followed for more than three years developed invasive breast carcinoma, all in the same breast with a previously detected DCIS. Average follow-up interval for the 18 women not developing invasive carcinoma was 16 years. The invasive carcinomas presented clinically from three to ten years (average, 6.1) after the biopsies demonstrating DCIS. Four women with invasive carcinoma developed distant metastases following mastectomy. This study suggests that 28% of women treated with biopsy only for DCIS presenting as an incidental histologic finding will develop invasive carcinoma in a follow-up period of approximately 15 years.

Intraductal carcinoma of the breast: Follow-up after biopsy only

The histological tumour type determined by current criteria has been investigated in a consecutive series of 1621 women with primary operable breast carcinoma, presenting between 1973 and 1987. All women underwent definitive surgery with node biopsy and none received adjuvant systemic therapy. Special types, tubular, invasive cribriform and mucinous, with a very favourable prognosis can be identified. A common type of tumour recognized by our group and designated tubular mixed carcinoma is shown to be prognostically distinct from carcinomas of no special type; it has a characteristic histological appearance and is the third most common type in this series. Analysis of subtypes of lobular carcinoma confirms differing prognoses. The classical, tubulo-lobular and lobular mixed types are associated with a better prognosis than carcinomas of no special type; this is not so for the solid variant. Tubulo-lobular carcinoma in particular has an extremely good prognosis similar to tumours included in the 'special type' category above. Neither medullary carcinoma nor atypical medullary carcinoma are found to carry a survival advantage over carcinomas of no special type. The results confirm that histological typing of human breast carcinoma can provide useful prognostic information.

Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up

In 110 consecutive, medicolegal autopsies of young and middle-aged women (range 20-54 years) the breasts were examined by an extensive histopathologic method and by correlative specimen radiography. Malignancy was found in 22 women (20%) of which only one was known to have had clinical invasive breast cancer (IBC). At autopsy 2 women had IBC (2%), the remaining in situ carcinoma (in situ BC) of microfocal type (18%), i.e. 15 (14%) intraductal carcinomas (DCIS), 4 (3%) lobular carcinoma in situ (LCIS) and one (1%) both DCIS and LCIS. Forty-five per cent of the women with malignancy had multicentric and 41% had bilateral lesions. Forty-five per cent of all histologically confirmed malignant lesions were identified by specimen radiography. Adenosis, benign epithelial hyperplasia, papilloma and duct ectasia were positively associated with malignancy. In addition malignancy was significantly more frequent among women aged more than 40 years, with late age at first full-term pregnancy, with alcohol abuse and with steatosis or cirrhosis of the liver. The results suggest that clinically occult in situ BC are frequent in young and middle-aged women.

Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies.

One hundred eighty-nine biopsies have been performed for clinically occult mammary lesions, detectable by mammography but not clinically apparent. Fifty-two cancers were demonstrated within this group, including 26 invasive ductal cancers, seven micro-invasive ductal cancers, 14 non-invasive ductal cancers, and five lobular carcinomas in situ. All mastectomy specimens were examined for multicentric foci of breast cancer in quadrants other than that in which the primary lesion was located. Of the invasive ductal cancers, 40% were multicentric. Of the micro-invasive ductal cancers, 57.1% were multi-centric. Of the non-invasive ductal cancers, 45.5% were multicentric. The one mastectomy specimen from a patient with lobular carcinoma in situ did not have evidence of residual disease. The overall incidence of multicentricity in the 43 specimens examined was 44.2%. These findings suggested that any therapeutic procedure for either invasive or non-invasive ductal carcinoma that does not include total mastectomy may leave behind foci of cancer, which are a threat to the patient.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819800615%2945%3A12%3C2913%3A%3AAID-CNCR2820451202%3E3.0.CO%3B2-0

Multicentricity of non-palpable breast cancer

Dual-energy mammography acquisition scenarios employing single-shot techniques are examined using computer simulation. A figure of merit of the signal-to-noise ratio squared over the glandular dose was chosen for the optimization task due to its exposure independence. Doses were evaluated using Monte Carlo techniques. The effects of kilovoltage, prepatient filtration, front detector thickness, mid-detector filtration thickness and composition were studied. Of the six detector pairs studied (Y2O2S/Gd2O2S, SrFBr/BaFBr, Y2O2S/LaOBr, Y2O2S/CaWO4, Y2O2S/YTaO4, and Y2O2S/LuTaO4), Y2O2S/Gd2O2S and SrFBr/BaFBr were found to be the best combinations. The effects of scatter and signal quantization were also examined. An alternative display technique whereby the tissue-subtracted (i.e., calcium) image is colorized and overlaid onto the conventional mammogram is introduced.

Dual-energy mammography: a detector analysis.

Breast cancer screening detected 139 biopsy-proved malignancies in 16,000 slef-selected women (8.7/1,000). In these, xeroradiography detected 78% (109), clinical examination 55% (76), and thermography 39% (54). In all 16,000 women, the thermogram was interpreted as positive in 17.9% (2,864). The greatest effectiveness of mammography vs. clinical examination was seen in detection of early breast cancers (small lesions with negative axillary lymph nodes). In this group, thermography was less effective than it was in patients with larger lesions and lymph node metastases.

Thermography, mammography, and clinical examination in breast cancer screening. Review of 16,000 studies.

Neural networks are a computer architecture, implementable in software or hardware, that allow an entirely new approach to the computerized perception of data. These so-called connectionist models are inspired by what is known about the architecture of biological neurons, in which the "intelligence" or processing capability of the network is a result of the interconnection strengths between large arrays of nonlinear processing nodes. Neural networks are described and then are used to analyze the common radiological problem of pattern recognition on a noisy background. Classical signal detection theory is used to compare network performance against that of human observers, using computer-generated sets of very simple "nodules." The neural network performed with better accuracy, relative to human observer performance, in the detection of this elementary test object. Although these results may not scale up with more complex images, the favorable performance of neural networks at this level suggests that further investigation is warranted.

Neural networks in radiology: An introduction and evaluation in a signal detection task

Breast cancer was detected in 156 of 17,526 asymptomatic women, (8.9/1000), aged 45-64 years, screened by mammography, thermography, and physical examination, Twenty-six percent of 149 pathologically reviewed cases metastasized to axillary nodes. Thirty-six percent of tumors were in situ, minimally invasive, or low grade tubular carcinomas, none of which metastasized. Increased rates of detection were shown for intraductal and tubular types. Frankly invasive ductal and lobular carcinomas had a mean diameter of 2.3 cm., 46% of which had axillary lymph node metastases. Seventy-percent of these were to only one to three nodes, however. Multicentricity with intraductal and lobular carcinoma in situ was frequently observed. Metastatic potential was related to tumor size, degree of stromal invasion, lymphatic permeation, and histologic grade. Few histological parameters other than size could be considered favorable. Forty-two percent of tumors were not palpable, the majority being in situ, minimally invasive, and tubular types. Only five nonpalpable invasive carcinomas metastasized. While the initial results of mass screening appear favorable, prolonged follow-up is needed to determine its impact on the population at risk.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%28197710%2940%3A4%3C1659%3A%3AAID-CNCR2820400440%3E3.0.CO%3B2-5

Gary S. Shaber

Papers

Multicentricity of non-palpable breast cancer

Dual-energy mammography: a detector analysis.

Thermography, mammography, and clinical examination in breast cancer screening. Review of 16,000 studies.

Neural networks in radiology: An introduction and evaluation in a signal detection task

The pathology of breast cancer detected by mass population screening.