Optimal Breast Density Characterization Using a Three-Dimensional Automated Breast Densitometry System
, Sadako Akashi-Tanaka 1, Misaki Matsuyanagi 1, Kanae Taruno 1, Terumasa Sawada 1, Akatsuki Kokaze 2 and Seigo Nakamura 1Round 1
Reviewer 1 Report
This is a case series of patients with known cancer where the role of MD assessment with Volpara and ultrasonography was examined.
The findings were that MG was less useful with higher MD, but that in patients with calcifications, MMG was more useful. US was equally useful in all densities
The authors use this information to propose that US be used in screening of those with high MD without malignant microcalcifications.
Interesting observation that those 50-59 had higher VDG than those >60. Worthy of comment as this is unexpected and different from other series, where older patients are found to have lower MD
The authors do not present details on how the diagnoses were reached. Were these symptomatic vs screen-detected, and how many had MRI as part of screening.
The other very important issue that is not mentioned is the Interval Cancer rate. This paper reports the non-detection (false negative) rate of MG and US in these patients who have been diagnosed, but the question of the patients with FN and no cancer diagnosed is not mentioned. While this cannot be addressed in this cohort/study design, it should be mentioned in the discussion
Statement that 10/192 with malignant calcifications were non-detected on MMG seems odd. The authors state that they had malignant calcifications – how were they ‘non-detected’?
The question of appropriate use of US is of importance worldwide. The authors suggest that those with high density but no malignant calcification are suitable for US. Most patients do not have calcifications, so does this mean that all patients with high MD should have US as screening? Adding US to those with malignant calcifications would not add many tests, and may provide clinically useful information. Is there any benefit to US in those with malignant calcifications?
The authors refer to the potential role of MRI and AB-MRI in screening. This section needs to be expanded, as results from the DENSE study suggest that MRI (or AB-MRI) may have a major role in those with high MD.
Lines 262-267 is difficult to understand. Needs to be re-written to clarify the meaning. I assume the authors mean ‘density’ when they use the word ‘concentration’…
Author Response
The authors do not present details on how the diagnoses were reached. Were these symptomatic vs screen-detected, and how many had MRI as part of screening.
Response: The route to the diagnoses has been added to table 1; no patients were observed via MRI screening; therefore, it is not listed.
The other very important issue that is not mentioned is the Interval Cancer rate. This paper reports the non-detection (false negative) rate of MG and US in these patients who have been diagnosed, but the question of the patients with FN and no cancer diagnosed is not mentioned. While this cannot be addressed in this cohort/study design, it should be mentioned in the discussion.
Response: As you have pointed out, this study design did not include patients with undiagnosed cancer or interval cancers. We have stated this as one of the limitations in the Discussion section.
Statement that 10/192 with malignant calcifications were nondetected on MMG seems odd. The authors state that they had malignant calcifications – how were they ‘non-detected’?
Response: These 10 cases were considered to belong to category 3 (malignant) when viewed in isolation, but to category 2 (benign) when compared over the years.
The question of appropriate use of US is of importance worldwide. The authors suggest that those with high density but no malignant calcification are suitable for US. Most patients do not have calcifications, so does this mean that all patients with high MD should have US as screening? Adding US to those with malignant calcifications would not add many tests, and may provide clinically useful information. Is there any benefit to US in those with malignant calcifications?
Response: As you pointed out, it is optimal to use combined ultrasound in all patients with hyperintense breasts. Combined ultrasound in patients with malignant calcification can provide clinically useful information. We have added a note to this effect in line 242-247.
The authors refer to the potential role of MRI and AB-MRI in screening. This section needs to be expanded, as results from the DENSE study suggest that MRI (or AB-MRI) may have a major role in those with high MD.
Response: Thank you for elucidating this clinical research. We have read the paper and cited it in the revised manuscript.
Lines 262-267 is difficult to understand. Needs to be re-written to clarify the meaning. I assume the authors mean ‘density’ when they use the word ‘concentration’…
Response: Thank you very much. We have rephrased it more concisely to improve clarity, per your suggestion.
Reviewer 2 Report
We thank the authors for this interesting study on mammography and ultrasound performance in breasts with different densities evaluated with Volpara software.
The work has a good general approach but some additions are needed before making it available for publication:
1) the purpose of the study is not clearly described
2) in the introduction you pointed out that in Asian countries the number of women with high density is greater than in Europeans and this is also reflected in your results. Since the higher density is also linked to a greater number of tumors we would expect to find a higher incidence rate of neoplasms than in Europe: do you have data on this? If you bring them back.
3) On some points you should integrate your bibliography a little with more recent works. Speaking of ABUS, I suggest you add this very recent study on over 1000 patients with dense breasts evaluated with mammography and ABUS:
- Gatta G. et al . Second-Generation 3D Automated Breast Ultrasonography (Prone ABUS) for Dense Breast Cancer Screening Integrated to Mammography: Effectiveness, Performance and Detection Rates. Pers. Med. 2021, 11, 875.
4) In the discussions there is no mention of CAD in mammography and the role of radiomics in the detection and characterization of breast lesions, the recent frontier opened by numerous studies that allow to increase diagnostic performance even in dense breasts. In this regard, I recommend that you integrate these themes into the discussion by adding these works to your bibliography:
- Massafra R. et al. Radiomic Feature Reduction Approach to Predict Breast Cancer by Contrast-Enhanced Spectral Mammography Images. Diagnostics 2021, 11, 684
Author Response
1) the purpose of the study is not clearly described
Response: We have rewritten the purpose of the study in the introduction to ensure conciseness and clarity.
2) in the introduction you pointed out that in Asian countries thenumber of women with high density is greater than in Europeansand this is also reflected in your results. Since the higher density
Response: We have added the reason for this to the Introduction section.
3)On some points you should integrate your bibliography a little with more recent works. Speaking of ABUS, I suggest you add this very recent study on over 1000 patients with dense breasts evaluated with mammography and ABUS:
- Gatta G. et al . Second-Generation 3D Automated Breast Ultrasonography (Prone ABUS) for Dense Breast Cancer Screening Integrated to Mammography: Effectiveness, Performance and Detection Rates. Pers. Med. 2021, 11, 875.
Response: Thank you for sharing these relevant papers. We have read and cited them in the revised manuscript.
4) In the discussions there is no mention of CAD in mammography and the role of radiomics in the detection and characterization of breast lesions, the recent frontier opened by numerous studies that allow to increase diagnostic performance even in dense breasts. In this regard, I recommend that you integrate these themes into the discussion by adding these works to your bibliography:
- Massafra R. et al. Radiomic Feature Reduction Approach to Predict Breast Cancer by Contrast-Enhanced Spectral Mammography Images. Diagnostics 2021, 11, 684
Response: Thank you for sharing these relevant papers. We have read and cited them in the revised manuscript.
Round 2
Reviewer 1 Report
The authors have addressed most of my concerns satisfactorily. The following should be addressed
Intro – line 18 – “density” rather than “concentration”
New para – line 41-44 – is unclear. The incidence of what is not so different between Asians and Europeans?
Line 45 – “Mammographic density” rather than “Mammary glands”
Line 48 – ‘varied’
Line 48 – Sentence commencing “additionally, …” should be moved to the end of the paragraph
Line 52 – “Mammographic density” rather than “Mammary gland density” This needs to be corrected throughout the manuscript
Line 108 – ‘surgery’ rather than ‘mastectomy’
Line 260 – needs re-writing. Is this about Contrast mammography, US, AI or radiomics? All 4 concepts are mentioned in the paragraph
Line 281 – “On the other hand,” should be removed from the sentence.
Line 265 - The fact that 8 cases were ‘accidentally’ detected on MRI warrants inclusion in the discussion around the potential role of (AB) MRI in screening.
Author Response
Intro – line 18 – “density” rather than “concentration”
Response: Thank you very much for this recommendation. The terminology has been revised as suggested.
New para – line 41-44 – is unclear. The incidence of what is not so different between Asians and Europeans?
Response: Thank you very much for this observation. I have made the appropriate corrections and clarifications.
Line 45 – “Mammographic density” rather than “Mammary glands”
Response: Thank you very much for this recommendation. The terminology has been revised as suggested.
Line 48 – ‘varied’
Response: Thank you very much for this recommendation. The phrase has been revised as suggested.
Line 48 – Sentence commencing “additionally, …” should be moved to the end of the paragraph
Response: Thank you very much for this helpful suggestion. I have made the appropriate corrections and clarifications, accordingly.
Line 52 – “Mammographic density” rather than “Mammary gland density” This needs to be corrected throughout the manuscript
Response: Thank you very much for this recommendation. The terminology has been revised as suggested.
Line 108 – ‘surgery’ rather than ‘mastectomy’
Response: Thank you very much for this recommendation. The terminology has been revised as suggested.
Line 260 – needs re-writing. Is this about Contrast mammography, US, AI or radiomics? All 4 concepts are mentioned in the paragraph
Response: Thank you very much for this observation. The phrasing has been revised to improve specificity(lines 286-290).
Line 281 – “On the other hand,” should be removed from the sentence.
Response: Thank you very much for this recommendation. The phrase has been removed as recommended.
Line 265 - The fact that 8 cases were ‘accidentally’ detected on MRI warrants inclusion in the discussion around the potential role of (AB) MRI in screening.
Response: Thank you very much for this suggestion. We have addressed this important point and included the associated content in the discussion (lines 281-283), per your suggestion.
