Evaluation of Adjuvant Treatments for Adenoid Cystic Carcinoma of the Breast: A Population-Based, Propensity Score Matched Cohort Study from the SEER Database

Round 1

Reviewer 1 Report

This is a large retrospektive study on Adenoidcystic carcinoma of the breast based on the SEER database. The study confirms the observations of other much smaller series that ACC is a triple negative tumor of good prognosis and chemotherapy does not influence the outcome; and also that histology grade (subtyping ACC) and node status are the most mportant prognostic factors.

Minor corrections are needed. 

- The proportion of ER positive cases is rather high, it needs a comment in the Discussion.

-The start search year in SEER is stated as 1975 in the text and 1979 in figure 1.

- I would skip words as extremely or surprisingly as the results confirm already published characteristics of ACC.

 

 

Author Response

Point 1: The proportion of ER positive cases is rather high, it needs a comment in the Discussion.

Response 1: Thanks very much for taking the time to review this manuscript. We appreciate all your comments and suggestions. In this study, 16.3% (169/1,036) of patients with ACC of the breast were ER-positive. The previous studies reported that the positive rate of ER in patients with this disease was about 15-18% which was consistent with the result of our study [1,2]. There was no difference in OS (Log-rank p=0.844) and BCSS (Log-rank p=0.382) between ER-positive and ER-negative patients with ACC of the breast. According to the multivariate analysis, HR status was not an independent prognostic factor for patients with ACC of the breast. Only a few patients have received endocrine therapy in the published studies [1,3]. Therefore the effect of endocrine therapy on ER-positive patients with ACC of the breast was also unclear. It is a pity that there has been no record of adjuvant endocrine therapy in the SEER database. More data need to report in the future. According to your suggestions, we have added the above comments to the discussion section of the manuscript (Line 376-386).

References

1. Nandini Kulkarni, Christopher M. Pezzi, Jon M. Greif, DO, et al. Rare Breast Cancer: 933 Adenoid Cystic Carcinomas from the National Cancer Data Base. Ann Surg Oncol (2013) 20:2236–2241.
2. Jia-Yuan Sun, San-Gang Wu, Shan-Yu Chen, et al. Adjuvant radiation therapy and survival for adenoid cystic carcinoma of the breast. Breast. 2017 Feb; 31:214-218.
3. Kaouthar Khanfir,Adel Kallel,Sylviane Villette,et al. Management of adenoid cystic carcinoma of the breast: a Rare Cancer Network study. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):2118-24.

 

Point 2: The start search year in SEER is stated as 1975 in the text and 1979 in figure 1.

Response 2: Thanks very much for taking the time to review this manuscript. We appreciate all your comments and suggestions. We are very sorry to admit the error in Figure 1: the correct year is 1975, not 1979. We have revised the year in Figure 1 and Table 3 (the year in the title).

 

Point 3: I would skip words as extremely or surprisingly as the results confirm already published characteristics of ACC.

Response 3: Thanks very much for taking the time to review this manuscript. We agree with your suggestions and will further explore this field in future research. Most previous studies observed the characteristics of ACC of the breast based on a small sample of single-center population, so the strength of evidence may be limited. A few studies based on public databases have also analyzed the relationship between survival and adjuvant treatments in patients with ACC of the breast, but most have focused on adjuvant radiotherapy. Our study was based on the SEER database, which not only analyzed the impact of adjuvant radiotherapy on survival but also analyzed the prognostic value of adjuvant chemotherapy. Additionally, the method of stratified analysis was also used to explore the possible effect modifiers. In terms of statistical analysis, the PSM method was used to match the patients according to clinicopathological characteristics, to better control underlying confounding factors. We sincerely accept your opinions and will conduct further studies on breast cancer with rare histological types in the future, especially those that are controversial in terms of adjuvant therapy. Thank you again for your suggestions.

Author Response File: Author Response.docx

Reviewer 2 Report

Overall, it is an interesting article. Needs some clarifications and editing of the language:

line 52-patients identified in database from 1975-2019, in diagram Fig. 1 1979-2019

Language editing needed- to suggest a few changes: 

Line 12: SEER ((Surveillance, Epidemiology, and End Results, 12 (SEER) the words first

Line 23: ACC of the breast cancer

line 56-57: to compared, which generally recognized

line 103: included  into in the

line 129-130: patients underwent received adjuvant CT

line 155: patients had dead had died for any reason

line 158: patients with who received adjuvant CT

line 166-167: underwent who received adjuvant RT // while compared with 19.8 y among patients who did not

line 208: was consistently favorable

line 210-211, 2013: nodal node negative

line 215: but not in patients who underwent BCT

lines 314-354: multiple language refinements needed

line 375:a great loss of missing data  ..... lacks lack of records

line 377: ACC was is a rare

Author Response

Point 1: line 52-patients identified in database from 1975-2019, in diagram Fig. 1 1979-2019.

Response 1: Thanks very much for taking the time to review this manuscript. We appreciate all your comments and suggestions. We are very sorry to admit the error in Figure 1: the correct year is 1975, not 1979. We have revised the year in Figure 1 and Table 3 (the year in the title).

Point 2: Language editing needed to suggest a few changes.

Response 2: Thanks very much for taking the time to review this manuscript. We are very sorry for the language problems in the manuscript and have made careful corrections according to your suggestions (shown in the table below). Thank you again for your caring advice.

Location	Before Correction	After Correction
Line 12	base on SEER	based on the SEER
Line 12-13	((Surveillance, Epidemiology, and End Results, SEER)	((Surveillance, Epidemiology, and End Results, SEER)
Line 20	According to univariate stratified analysis	According to the univariate stratified analysis
Line 22	From multivariate analysis	From the multivariate analysis
Line 24	ACC of the breast cancer	ACC of the breast cancer
Line 25	for patient with this disease	for patients with this disease
Line 33-34	oncologists often take histological types into consideration	oncologists often take consider histological types into consideration
Line 42	is triple-negative subtype	is triple-negative subtype
Line 52	based on SEER database	based on the SEER database
Line 55	records on live status	records on the live status
Line 56	In order to compared survival	In order to To compared survival
Line 57	histological types which generally recognized with a favourable prognosis	histological types which generally recognized with a favourable prognosis
Line 61	extracted from SEER	extracted from the SEER
Line 65	ER-positive and/or PR-positive was then	ER-positive and/or PR-positive was were then
Line 69	from SEER database	from the SEER database
Line 71	on live status	on the live status
Line 81	in matching model	in the matching model
Line 81	Balance between the two groups	The balance between the two groups
Line 83	Chi square test	Chi-square test
Line 83	t test	t-test
Line 87	as percentage	as percentages
Line 91	survival rate were estimated	survival rates were estimated
Line 94	Factors showed	Factors that showed
Line 95	or considered clinically relevant	or were considered clinically relevant
Line 96	into multivariate COX	into the multivariate COX
Line 104	included into analyses	included into the analyses
Figure 1	1979-2019	1975-2019
Line 125	Patient with ACC of the breast	Patients with ACC of the breast
Line 128	half of patients	half of the patients
Line 131	99 patients underwent	99 patients underwent received
Line 134	treatments is listed	treatments is are listed
Line 158	patients had dead for any reason	patients had dead died for any reason
Line 161	Patients with adjuvant CT	Patients with who received adjuvant CT
Line 163-164	characteristics of ... is listed in Table S1	characteristics of ... is are listed in Table S1
Line 167	after matching procedure	after the matching procedure
Line 169	patients underwent adjuvant RT	patients underwent who received adjuvant RT
Line 170	while 19.8 years among patients did not	While compared with 19.8 years among patients who did not
Line 174-175	characteristics of ... is listed in Table S2	characteristics of ... is are listed in Table S2
Line 177	after matching procedure	after the matching procedure
Line 213	was consistent favorable	was consistently favorable
Line 215-216, 219	nodal negative	nodal node negative
Line 220	patients underwent BCS	patients who underwent BCS
Line 252	apart for Her2 status	apart for from Her2 status
Line 281	The following two factors	The following two factors
Line 283	Adjuvant CT, as well as adjuvant RT,	Adjuvant CT, as well as adjuvant and RT,
Line 284	on multivariate models	on the multivariate models
Line 293-294	from SEER database between 1979 and 2019	from the SEER database between 1979 1975 and 2019
Line 321	after matching procedure	after the matching procedure
Line 324	presented almost triple-negative molecular subtype	presented an almost triple-negative molecular subtype
Line 328	ACC of breast	ACC of the breast
Line 329	5-year and 10-year BCSS rate 95.3% and 92.6%	5-year and 10-year BCSS rates of 95.3% and 92.6%
Line 331	which was a favourable histology	which was a favourable histology
Line 332	Since its rarity	Since Given its rarity
Line 335	ACC of breast	ACC of the breast
Line 336	Among 1,036 included patients from SEER database	Among 1,036 included patients from in the SEER database
Line 339	a negative attitude of physician	a negative attitude of physicians
Line 341	vast majority of patients	the vast majority of patients
Line 342	nodal negative	nodal node negative
Line 346	adjuvant was not necessary	Adjuvant CT was not necessary
Line 350	adjuvant CT could optimize prognosis	adjuvant CT could optimize the prognosis
Line 352	nodal positive	nodal node positive
Line 354-355	younger age, higher histology grade, larger tumor size, nodal involved and ER-negative	younger age, higher histology grade, larger tumor size, nodal involved, and ER-negative
Line 358	failed to improved	failed to improved
Line 361	Among 1,036 patients included from SEER database, 422 underwent adjuvant RT	Among 1,036 patients included from in the SEER database, 422 underwent received adjuvant RT
Line 364-365	The role of adjuvant RT of locoregional control	The role of adjuvant RT of in locoregional control
Line 365	still remained unclear	still remained unclear
Line 370	SEER database	the SEER database
Line 370	the results of univariate stratified analysis	the results of the univariate stratified analysis
Line 374	current guideline recommended	the current guidelines recommended
Line 390	from SEER database	from the SEER database
Line 392-393	The second were limitations in the SEER database, for example, a great loss of Her2 expression and lacks records of other adjuvant treatments such as endocrine therapy.	The second were was limitations in the SEER database, for example, a great loss of missing data on Her2 expression and lacks records of other adjuvant treatments such as endocrine therapy.
Line 394	ACC was a rare histological type	ACC was is a rare histological type
Line 446	https://www.nccn.org/	hHttps://www.nccn.org/

Author Response File: Author Response.docx