- Top of page
- Materials and Methods
- Disclosure Statement
The present study retrospectively evaluated the mammographic findings of 606 Japanese women with breast cancer (median age 50 years; range 27–89 years) and correlated them with histopathological characteristics. Mammographic findings were evaluated with an emphasis on mass shape, margin, density, calcification, and the presence of architectural distortion; these findings were correlated with histopathological characteristics such as intrinsic subtype, histological grade, lymphovascular invasion, and the Ki-67 labeling index. An irregular mass shape and masses with a spiculated margin were significantly higher in the group of patients with luminal A breast cancer than in patients with masses that were lobular or round, or in tumors with an indistinct or microlobulated periphery (P = 0.017, P = 0.024, P < 0.001, and P = 0.001, respectively). Irregular mass shape and spiculated periphery were significantly lower in patients with Grade 3 cancer (P < 0.001 for both). In terms of lymphovascular invasion, there were significant differences between oval and irregular or round mass shape (P = 0.008 and P = 0.034), between tumors with a microlobulated and indistinct periphery (P = 0.014), between tumors with a punctate and amorphous or pleomorphic calcification shape (P = 0.030 and 0.038), and between the presence and absence of architectural distortion (P = 0.027). Equivalent or low-density masses were also higher in Grade 1 breast cancers (P = 0.007). There were significant differences in the Ki-67 labeling index between irregular and lobular or round tumors (P < 0.001 and P = 0.014), as well as between spiculated and indistinct or microlobulated tumors (P < 0.001 for both). Significant differences were noted in the mammographic features of different primary breast cancer subtypes. These proposed mammographic diagnostic criteria based on biological characteristics may contribute to a more accurate prediction of biological behavior of breast malignancies. (Cancer Sci 2011; 102: 2179–2185)
The incidence of breast cancer has increased worldwide, which is considered due, in part, to mass screening programs resulting in the discovery of clinically occult breast lesions. Mammographic screening has been demonstrated to reduce breast cancer mortality in both Western and Oriental populations.(1) This mortality may be as great as 63% in women attending for screening.(2) Therefore, million of mammographic examinations are being performed yearly worldwide, and mammography has become the gold standard for detecting breast disorders. Strict attention to high-quality interpretation is required for successful of a mammographic diagnosis. Thus, it is important to establish an accurate diagnostic system for mammography.
Traditionally, prognostic determinations are made mainly on the basis of pathological information, including histological grade and lymphovascular invasion.(3–5) In addition to histological information, the status of molecular markers that have prognostic and predictive value can contribute to the selection of an optimal treatment strategy. These markers include estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) and determining the status of these markers has become standard practice in the management of breast cancer because ER and HER2 positivity can predict a patient’s response to endocrine therapy or targeted therapy with monoclonal antibodies directed against HER2.(6) In addition, the St Gallen international expert consensus meeting on the primary treatment of early breast cancer reported that features indicative of increased risk of recurrence, thus indirectly supporting the addition of chemotherapy to endocrine therapy, include lower expression of steroid hormone receptors, Grade 3 tumors, high proliferation (as measured by conventional or multigene assays), and extensive peritumoral vascular invasion.(7) However, these therapeutic determinations have been derived mainly from pathological information.
The appearance of tumors on mammograms has a generally good correlation with subsequent histological characteristics. For example, microcalcification is the hallmark of ductal carcinoma in situ;(8) spiculation is significantly correlated with low histologic grade; and ill-defined masses and microcalcifications are features of high-grade tumors.(8) Accurate correlation of mammographic findings with corresponding histopathologic features is considered one of the most important aspects of mammographic evaluation. Full histopathological information, including histological grades and intrinsic subtypes, is determined correctly after surgery.(9) Therefore, the purpose of the present study was to retrospectively evaluate mammographic findings and to compare the histopathological characteristics of the different tumors (i.e. intrinsic subtype, histological grade, lymphovascular invasion, and Ki-67 labeling index) in Japanese patients.
- Top of page
- Materials and Methods
- Disclosure Statement
Histological grade is well known to have a strong correlation with clinical outcome in patients with breast cancer.(4) Accumulating clinical evidence suggests that prognostic factors influencing breast cancer extend beyond the traditional tumor histological grade.(17) Several factors, including ER expression, HER2 status, and lymphovascular invasion, have been clearly demonstrated in recent years to contribute significantly to the management and subsequent prognosis of patients with breast cancer.(7,18) Therefore, an accurate correlation between mammographic findings and their corresponding histopathological features is considered most important in mammographic evaluation. Mammographic findings may provide insights into pathological and biological features, including tumor cell characteristics, histological grade, and cell proliferation. We attempted to determine which finding is more relevant with regard to the newly defined subtype of breast carcinoma cells. Therefore, the purpose of the present study was to evaluate the correlation between mammographic findings (e.g. mass shape, margin, density, calcification shape, FAD, and the presence of architectural distortion) with intrinsic subtype, histological grade, lymphovascular invasion, and the Ki-67 labeling index in breast cancer patients.
Several previous studies evaluated the correlation between mammographic findings and histopathological characteristics in individual patients.(8,19–21) A number of independent groups demonstrated that masses with a spiculated periphery were associated with a good outcome in patients.(19,20) Conversely, well-defined masses were associated with triple-negative breast cancer.(8,21) The results of the present study demonstrate that is a higher incidence of lower histological grade in masses with an irregular shape and/or spiculated margins, although a higher histological grade is not necessarily associated with irregular mass shape or spiculated margins. In addition, correlation of mammographic findings with the intrinsic subtype demonstrated that irregular mass shape and/or spiculated margin masses were significantly more frequently detected in luminal A breast cancers than in the other subtypes in this cohort of Japanese patients. However, oval and round mass shape and/or indistinct and microlobulated margin masses were significantly more frequently detected in triple-negative breast cancers or HER breast cancers. As for architectural distortion, the ratio of architectural distortion was significantly higher in luminal A cases and also tended to be associated with histological Grade 1. Together, these results suggest that poorly differentiated breast carcinoma cells are associated with good histological grade and luminal A subclassification. However, well-differentiated carcinoma cells are associated with adverse clinical grading and negative ER status.
Previous studies have demonstrated that these differentiations were related somewhat with adhesion factors.(22,23) Loss of adhesion factors in carcinoma cell is considered to play a role in the characteristic histological appearance of invasive carcinoma as loosely dispersed linear columns of cells and a typical discrete mass.(22) This more diffuse infiltrative pattern may explain some of the typical imaging appearances of tumors, such as spiculation and distortion.(22) In addition, adhesion factors are correlated with high histologic grade.(23) Therefore, adhesion factors may be considered to be correlated with the results of the present study in that spiculated breast cancers have a good clinical outcome and histological Grade 1. However, it is also true that numerous biological mechanisms underlying the association between the process of infiltration and histopathological characteristics remain unknown and that further investigations are required to confirm interpretation of mammography in terms of the biological and histopathologic characteristics of tumors.
To the best of our knowledge, this is the first study to compare mammographic findings with the Ki-67 labeling index and histopathological lymphovascular invasion. The results of the present study demonstrated that there was a higher incidence of a lower Ki-67 labeling index in tumors with an irregular mass shape, spiculated periphery, and equivalent or low mass density. Irregular mass shape and a spiculated periphery are well-known predictors of malignancy, but the results of the present study seem to suggest that findings of irregular shape and a spiculated periphery are relatively good prognostic predictors in terms of the Ki-67 labeling index. In addition, the results of the present study demonstrate that lymphovascular invasion was significantly greater in cases in which there was architectural distortion; however, the incidence of lymphovascular invasion was not significantly higher in spiculated masses. These results all suggest that the correlation between findings of radiological distortion and the mechanisms of lymphovascular invasion remain unknown and further investigations are required.
We also examined the correlation between mammographic calcification shape and histopathological characteristics. Previous studies have reported that triple-negative breast cancers are more likely to exhibit comedo calcifications.(8) In addition, the high frequency of comedo calcification in triple-negative breast cancers may represent a consequence of high histologic grade.(8) The presence of mammographic comedo calcification has also been reported to be associated with a poor prognosis in small screening-detected invasive cancers.(19) The results of the present study also demonstrate that non-necrotic calcifications, including amorphous and punctate calcification, are associated with a higher ratio of luminal A cases, whereas necrotic calcifications, including pleomorphic and linear calcification, were associated with a higher ratio of HER breast cancers. In addition, necrotic calcifications tended to be associated with a higher histological grade than non-necrotic calcifications. Therefore, the results suggest that the type of calcification may become a prognostic factor for breast malignancies.
We noted significant differences in the mammographic features of different primary breast cancer immunophenotypes in the present study. Stratifying the mammographic features according to immunophenotypes reveals distinct differences among cancer subtypes. However, the limitations of the present study include that fact that the study was retrospective in nature and was performed in a single institute, namely Tohoku University Hospital. Therefore, further investigations are needed, including analysis in several different institutions to further refine the new mammographic criteria. Biological and histopathological differences may result in imaging differences that may help us better understand the development of breast cancer. These proposed mammographic diagnostic criteria based on biological characteristics may contribute to a more accurate prediction of the biological behavior of breast malignancies.