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Mammographic Breast Density and Subsequent Risk of Breast Cancer in Postmenopausal Women According to the Time Since the Mammogram
Mammographic Breast Density and Subsequent Risk of Breast Cancer in Postmenopausal Women According to the Time Since the Mammogram Yaghjyan L, Colditz GA, Rosner B, et al (Washington Univ in St. Louis, MO; Brigham; Women’s Hosp and Harvard Med School, Boston, MA) Cancer Epidemiol Biomarkers Prev 22:11101117, 2013
Background.dFew studies have shown that the association between mammographic breast density and breast cancer persists for up to 10 years after the mammogram. We investigated associations of percent density, absolute dense, and nondense areas with breast cancer risk according to the time since the mammogram. Methods.dThis study included 1,028 incident breast cancer cases diagnosed within the Nurses’ Health Study and 1,780 matched controls. Breast density was measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from the biennial questionnaires before the date of cancer diagnosis for cases and their matched controls. The data were analyzed with logistic regression. Results.dBreast cancer risk increased with increasing percent density and increasing absolute dense area and decreased with increasing nondense area. In multivariate analysis, the magnitude of the association between percent density and breast cancer was similar when the time since the mammogram was <2, 2 to <5, and 5 to <10 years [density $50% vs. <10%: ORs, 3.12; 95% confidence interval (CI): 1.55e6.25, 5.35 (95% CI: 2.93e9.76), and 3.91 (95% CI: 2.22e6.88), respectively]. Similarly, the magnitude of association between
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quartiles of dense and nondense areas and breast cancer risk were similar across the time strata. We found no interactions between the time since the mammogram and breast density measures (Pinteraction > 0.05). Conclusions.dPatterns of the associations between percent density, absolute dense, and nondense area with breast cancer risk persist for up to 10 years after the mammogram. Impact.dA one-time density measure can be used for long-term breast cancer risk prediction. Mammographic breast density has become a widely discussed topic in medical and legislative arenas. At least 10 states mandate that women who are found to have dense breasts via screening mammography be notified in writing of that fact. Many other states are considering legislative efforts. Therefore, any discussion of breast density and breast cancer risk is timely. How breast density changes over time is a topic of interest, and this article by Yaghjyan and colleagues perhaps touches on that issue by looking at long-term risk after a density determination on “the mammogram.” “The mammogram” is a phrase often repeated throughout this article. It is defined as the mammogram obtained “closest to the time of blood collection from 1,305 breast cancer cases. and 2,362 case matched controls.” Only those who were postmenopausal at the time of the mammogram and “reference date” were included. Only 1 breast density determination was recorded; presumably, the women had other mammograms during the study period, but these were not analyzed, and the average time between “the mammogram” and cancer diagnosis was 4.8 years. Did the risk conferred by breast density stay the same in women whose breasts retained the same density over the next decade compared with women whose breast tissue involuted?
Breast Diseases: A Year BookÒ Quarterly Vol 24 No 4 2014
How breast density is determined and the magnitude of the risk that density confers are topics of discussion. The majority of the United States uses the 4 Breast Imaging-Reporting and Data System (BI-RADS) categories: fatty, scattered fibroglandular elements, heterogeneously dense, and extremely dense. The authors of this article, however, did not use the almost universal density scores; instead, they employed a computer-determined breast density measurement that lumped heterogeneously dense and extremely dense breasts into 1 category. As those with extremely dense breasts have the highest risk, it is interesting to ponder why this was done. Likewise, can we learn anything from the group with less than 10% density? Could one suggest that this cohort have less frequent mammograms? The article discusses how breast cancers were detected: 60% were detected by screening mammography and the remaining 40% by physical examination, including that provided by a clinician, the patient, or significant other. Ultrasound or magnetic resonance imaging screening is not mentioned in this work. The reader must assume that patients were not told of their density or offered supplemental screening. It would be interesting to know if there were statistically significant stage differences between the cancers detected by screening and those detected by physical examination. Density did not seem to make a difference in the mode of detection. Perhaps, however, if supplemental screening had been offered and used, some of the palpable cancers would have been detected. Likewise, the mammograms appear to have been analog mammograms, which are less sensitive than digital mammograms for patients with dense breasts. The authors make an interesting statement in the discussion: “.the BI-RADS measurement is primarily
used to alert radiologists about lower sensitivity of mammography in women with dense breasts rather than for risk assessment.” It is not the radiologist who alerts himself or herself about lower sensitivity, but the BI-RADS density classification is put in the report to alert the non-radiologist reader about the relative sensitivity of
the study as well as relative risk. That information is often conveyed to the patient, sometimes in writing using state-mandated language, and the patient may be offered supplemental screening examinations, such as ultrasound. This is an impressive study of postmenopausal women and breast
density. It shows that a single mammographic breast density measurement can be used to assess relative risk over the next decade of a woman’s life.
Magnetic Resonance Imaging as a Predictor of Pathologic Response in Patients Treated With Neoadjuvant Systemic Treatment for Operable Breast Cancer: Translational Breast Cancer Research Consortium Trial 017
Tumors were characterized by immunohistochemical phenotype into 4 categories based on receptor expression: hormone (estrogen and progesterone) receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n ¼ 327), HRpositive/HER2-positive, (n ¼ 148), HRnegative/HER2-positive, (n ¼ 101), and triple-negative (HR-negative/HER2 negative; n ¼ 155). In all, 194 of 249 patients (78%) with HER2-positive tumors received trastuzumab. Univariate and multivariate analyses of factors associated with radiographic complete response (rCR) and pCR were performed. Result.dFor the total group, the rCR and pCR rates were 182 of 746 patients (24%) and 179 of 746 patients (24%), respectively, and the highest pCR rate was observed for the triplenegative subtype (57 of 155 patients; 37%) and the HER2-positive subtype (38 of 101 patients; 38%). The overall accuracy of MRI for predicting pCR was 74%. The variables sensitivity, negative predictive value, positive predictive value, and accuracy differed significantly among tumor subtypes, and the greatest negative predictive value was observed in the triple-negative (60%) and HER2-positive (62%) subtypes. Conclusions.dThe overall accuracy of MRI for predicting pCR in invasive breast cancer patients who
were receiving NCT was 74%. The performance of MRI differed between subtypes, possibly influenced by differences in pCR rates between groups. Future studies will determine whether MRI in combination with directed core biopsy improves the predictive value of MRI for pathologic response.
De Los Santos JF, Cantor A, Amos KD, et al (Univ of Alabama at Birmingham Comprehensive Cancer Ctr; Univ of North Carolina Chapel Hill; et al) Cancer 119:1776-1783, 2013
Background.dIncreased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer have prompted interest in whether patients who achieved a pCR can be identified preoperatively and potentially spared the morbidity of surgery. The objective of this multicenter, retrospective study was to estimate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting a pCR in the breast. Methods.dMRI studies at baseline and after the completion of NCT plus data regarding pathologic response were collected retrospectively from 746 women who received treatment at 8 institutions between 2002 and 2011.
L. Margolies, MD, FACR
For inoperable cancers, NCT is the standard of care. Because women have become more aware of the importance of early diagnosis, and because of the wide availability of screening programs, the diagnosis of inoperable locally advanced breast cancer has been reduced, but the use of NCT has been greatly increased. It has evolved and become an important treatment modality for immediately operable cancers. Very effective chemotherapy and targeted therapy regimens are available, and many patients can achieve pCR, which raises a question about the optimal surgery and radiotherapy protocol that can be offered to a patient after the completion of NCT. If a patient achieves pCR, she may be treated safely with radiation alone without surgery. However, previous studies in patients who showed a complete clinical remission revealed a higher locoregional recurrence rate in the no-surgery group than in the surgery group.1
Breast Diseases: A Year BookÒ Quarterly Vol 24 No 4 2014
343
Background.dFew studies have shown that the association between mammographic breast density and breast cancer persists for up to 10 years after the mammogram. We investigated associations of percent density, absolute dense, and nondense areas with breast cancer risk according to the time since the mammogram. Methods.dThis study included 1,028 incident breast cancer cases diagnosed within the Nurses’ Health Study and 1,780 matched controls. Breast density was measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from the biennial questionnaires before the date of cancer diagnosis for cases and their matched controls. The data were analyzed with logistic regression. Results.dBreast cancer risk increased with increasing percent density and increasing absolute dense area and decreased with increasing nondense area. In multivariate analysis, the magnitude of the association between percent density and breast cancer was similar when the time since the mammogram was <2, 2 to <5, and 5 to <10 years [density $50% vs. <10%: ORs, 3.12; 95% confidence interval (CI): 1.55e6.25, 5.35 (95% CI: 2.93e9.76), and 3.91 (95% CI: 2.22e6.88), respectively]. Similarly, the magnitude of association between
342
quartiles of dense and nondense areas and breast cancer risk were similar across the time strata. We found no interactions between the time since the mammogram and breast density measures (Pinteraction > 0.05). Conclusions.dPatterns of the associations between percent density, absolute dense, and nondense area with breast cancer risk persist for up to 10 years after the mammogram. Impact.dA one-time density measure can be used for long-term breast cancer risk prediction. Mammographic breast density has become a widely discussed topic in medical and legislative arenas. At least 10 states mandate that women who are found to have dense breasts via screening mammography be notified in writing of that fact. Many other states are considering legislative efforts. Therefore, any discussion of breast density and breast cancer risk is timely. How breast density changes over time is a topic of interest, and this article by Yaghjyan and colleagues perhaps touches on that issue by looking at long-term risk after a density determination on “the mammogram.” “The mammogram” is a phrase often repeated throughout this article. It is defined as the mammogram obtained “closest to the time of blood collection from 1,305 breast cancer cases. and 2,362 case matched controls.” Only those who were postmenopausal at the time of the mammogram and “reference date” were included. Only 1 breast density determination was recorded; presumably, the women had other mammograms during the study period, but these were not analyzed, and the average time between “the mammogram” and cancer diagnosis was 4.8 years. Did the risk conferred by breast density stay the same in women whose breasts retained the same density over the next decade compared with women whose breast tissue involuted?
Breast Diseases: A Year BookÒ Quarterly Vol 24 No 4 2014
How breast density is determined and the magnitude of the risk that density confers are topics of discussion. The majority of the United States uses the 4 Breast Imaging-Reporting and Data System (BI-RADS) categories: fatty, scattered fibroglandular elements, heterogeneously dense, and extremely dense. The authors of this article, however, did not use the almost universal density scores; instead, they employed a computer-determined breast density measurement that lumped heterogeneously dense and extremely dense breasts into 1 category. As those with extremely dense breasts have the highest risk, it is interesting to ponder why this was done. Likewise, can we learn anything from the group with less than 10% density? Could one suggest that this cohort have less frequent mammograms? The article discusses how breast cancers were detected: 60% were detected by screening mammography and the remaining 40% by physical examination, including that provided by a clinician, the patient, or significant other. Ultrasound or magnetic resonance imaging screening is not mentioned in this work. The reader must assume that patients were not told of their density or offered supplemental screening. It would be interesting to know if there were statistically significant stage differences between the cancers detected by screening and those detected by physical examination. Density did not seem to make a difference in the mode of detection. Perhaps, however, if supplemental screening had been offered and used, some of the palpable cancers would have been detected. Likewise, the mammograms appear to have been analog mammograms, which are less sensitive than digital mammograms for patients with dense breasts. The authors make an interesting statement in the discussion: “.the BI-RADS measurement is primarily
used to alert radiologists about lower sensitivity of mammography in women with dense breasts rather than for risk assessment.” It is not the radiologist who alerts himself or herself about lower sensitivity, but the BI-RADS density classification is put in the report to alert the non-radiologist reader about the relative sensitivity of
the study as well as relative risk. That information is often conveyed to the patient, sometimes in writing using state-mandated language, and the patient may be offered supplemental screening examinations, such as ultrasound. This is an impressive study of postmenopausal women and breast
density. It shows that a single mammographic breast density measurement can be used to assess relative risk over the next decade of a woman’s life.
Magnetic Resonance Imaging as a Predictor of Pathologic Response in Patients Treated With Neoadjuvant Systemic Treatment for Operable Breast Cancer: Translational Breast Cancer Research Consortium Trial 017
Tumors were characterized by immunohistochemical phenotype into 4 categories based on receptor expression: hormone (estrogen and progesterone) receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n ¼ 327), HRpositive/HER2-positive, (n ¼ 148), HRnegative/HER2-positive, (n ¼ 101), and triple-negative (HR-negative/HER2 negative; n ¼ 155). In all, 194 of 249 patients (78%) with HER2-positive tumors received trastuzumab. Univariate and multivariate analyses of factors associated with radiographic complete response (rCR) and pCR were performed. Result.dFor the total group, the rCR and pCR rates were 182 of 746 patients (24%) and 179 of 746 patients (24%), respectively, and the highest pCR rate was observed for the triplenegative subtype (57 of 155 patients; 37%) and the HER2-positive subtype (38 of 101 patients; 38%). The overall accuracy of MRI for predicting pCR was 74%. The variables sensitivity, negative predictive value, positive predictive value, and accuracy differed significantly among tumor subtypes, and the greatest negative predictive value was observed in the triple-negative (60%) and HER2-positive (62%) subtypes. Conclusions.dThe overall accuracy of MRI for predicting pCR in invasive breast cancer patients who
were receiving NCT was 74%. The performance of MRI differed between subtypes, possibly influenced by differences in pCR rates between groups. Future studies will determine whether MRI in combination with directed core biopsy improves the predictive value of MRI for pathologic response.
De Los Santos JF, Cantor A, Amos KD, et al (Univ of Alabama at Birmingham Comprehensive Cancer Ctr; Univ of North Carolina Chapel Hill; et al) Cancer 119:1776-1783, 2013
Background.dIncreased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer have prompted interest in whether patients who achieved a pCR can be identified preoperatively and potentially spared the morbidity of surgery. The objective of this multicenter, retrospective study was to estimate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting a pCR in the breast. Methods.dMRI studies at baseline and after the completion of NCT plus data regarding pathologic response were collected retrospectively from 746 women who received treatment at 8 institutions between 2002 and 2011.
L. Margolies, MD, FACR
For inoperable cancers, NCT is the standard of care. Because women have become more aware of the importance of early diagnosis, and because of the wide availability of screening programs, the diagnosis of inoperable locally advanced breast cancer has been reduced, but the use of NCT has been greatly increased. It has evolved and become an important treatment modality for immediately operable cancers. Very effective chemotherapy and targeted therapy regimens are available, and many patients can achieve pCR, which raises a question about the optimal surgery and radiotherapy protocol that can be offered to a patient after the completion of NCT. If a patient achieves pCR, she may be treated safely with radiation alone without surgery. However, previous studies in patients who showed a complete clinical remission revealed a higher locoregional recurrence rate in the no-surgery group than in the surgery group.1
Breast Diseases: A Year BookÒ Quarterly Vol 24 No 4 2014
343