Loading

Impact of Genetic Testing on Breast Cancer Surgery: Are the Variants Significant?

Research Article | Open Access Volume 5 | Issue 1 |

  • 1. Department of Breast Surgical Oncology, Orlando Health UF Health Cancer Center, USA
  • 2. Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, USA
  • 3. Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, USA
+ Show More - Show Less
Corresponding Authors
Christine Laronga, Department of Breast Oncology, H. Lee Moffitt Cancer Center and Research Institute, 10920 N. McKinley Drive, Tampa, FL 33612, USA, Tel: 1-813-745-2480; Fax: 1-813-745-728
Abstract

Background: With increasing variant of unknown significance (VUS) genetic testing (GT) results, we evaluated the significance on surgical management for breast cancer patients.

Methods: Patients from an IRB-approved database recruited from November 2000 to January 2017 with a VUS and history of breast cancer were identified. Self-reported questionnaire data was collected. Groups were compared using Chi-square, Fisher’s Exact or Kruskal-Wallis test by surgical type and timing of GT.

Results: Seventy-nine VUS patients with breast cancer and questionnaire data were identified and studied. Initial surgical management was: 35 (44%) lumpectomies, 15 (19%) unilateral mastectomies and 29 (37%) bilateral mastectomies. Fifteen (19%) patients with bilateral breast cancer were excluded from analyses. Patients with VUS diagnosis before surgery, chose contralateral prophylactic mastectomy (CPM) more than diagnosis after surgery, but it was not statistically significant (50% vs 32%, p=0.215).

Conclusions: A VUS influences, but not statistically significantly, surgical decision making. Appropriateness for CPM should not rely on a VUS result.

Keywords

• Genetic Testing; Variant of Unknown Significance; 
Surgical Decision Making; Bilateral Mastectomy; 
Contralateral Prophylactic Mastectomy

Citation

Henry D, Lee M, Almanza D, Sun W, Boulware D, et al. (2018) Impact of Genetic Testing on Breast Cancer Surgery: Are the Variants Significant? JSM Genet Genomics 5(1): 1028.

ABBREVIATIONS

NCCN: National Comprehensive Cancer Network; VUS: Variant of Unknown Significance; ASCO: American Society of Clinical Oncology; RRM: Risk Reducing Mastectomy; ICARE: Inherited Cancer Registry; TM: Therapeutic Mastectomy; CPM: Contralateral Prophylactic Mastectomy

INTRODUCTION

A hereditary cause of breast cancer is suggested when multiple family members have developed breast and/or other cancers with an autosomal dominant inheritance pattern [1]. The recognition of an autosomal dominant pattern of breast cancer in families led to the discovery of the breast cancer susceptibility genes, BRCA1 and later BRCA2, in the 1990s [2-5]. When BRCA testing became commercially available in 1996, the American Society of Clinical Oncology released a consensus statement that genetic testing is recommended when three criteria are met: a personal or family history suggesting genetic cancer susceptibility, adequate interpretation of the test results, and the results will aid in the diagnosis or influence medical or surgical management of the patient or family members at risk for cancer [1,6].

Since that time, due to the end of the BRCA testing patent and advancements in genomic sequencing, we are able to offer more affordable and timelier testing. Although hereditary breast cancer still only accounts for approximately 5-10% of all breast cancers, within this minority we are now able to test for additional heritable genes that portend an increased risk for breast cancer when altered (pathogenic mutations) [1,7]. The use of multigene panel tests is increasing and the genetic testing landscape continues to evolve [8]. Based on the National Comprehensive Cancer Network (NCCN) guidelines, the most clinically relevant genes for an increased risk of breast cancer include: BRCA1, BRCA2, PTEN, TP53, ATM, CDH1, CHEK2, NBN, NF1, PALB2 and STK11 [9]. With more genes identified and varied implications of each mutation, American Society of Clinical Oncology (ASCO) updated the guidelines in 2010 to include the addition of genetic counseling with genetic testing [10].

Genetic counseling is essential for accurate interpretation of genetic testing results. This is especially important when testing for multiple genes, since there is a higher chance of getting a variant of unknown significance (VUS) [9,11]. A VUS is a mutation identified in a gene that has an unknown effect on protein function [12]. Currently not much is known about a VUS in regards to clinical significance, which creates a counseling dilemma. As a result, a VUS is treated as a negative result. Overtime, a VUS can be reclassified definitely as a benign polymorphism (negative result) that is unrelated to an increased breast cancer risk. A VUS can also later be reclassified as a pathogenic mutation and indicate higher risk. Most reclassifications represent the former, with only 1-6% of VUS being reclassified as pathogenic [13,14]. Given the aforementioned, other factors that may make a person at an increased risk for the development of breast cancer should be considered in addition to a VUS result, such as a personal and/ or family cancer history. These things may be more consistent with an familial cancer syndrome, and not simply the genetic testing results [15]. It is important to note that validated risk stratification models, such as the Gail Model and Tyrer-Cuzick, are not applicable to patients who have already been diagnosed with breast cancer, as they are intended for unaffected patients with multiple risk factors for breast cancer [16,17].

A patient may undergo genetic testing at one of three different time points in their lifetime: unaffected, after diagnosis of breast cancer but before definitive treatment, or after diagnosis and definitive treatment. The most immediate implications are among those who undergo testing after diagnosis but before definitive treatment [2]. When testing yields a positive (pathogenic) result, these results are associated with causing cancer. Risk-reducing surgery, such as risk-reducing mastectomy (RRM), has been shown to significantly reduce the risk of developing a contralateral breast cancer and improve overall survival in carriers of BRCA1 and BRCA 2 pathogenic mutations [1]. However, these risk reducing surgical benefits have not been proven for patients with a VUS.

A number of factors contribute to a patient’s surgical decision making. Current trends suggest genetic testing makes a significant impact in surgical decision making, and not always appropriately. Kurian et al., showed that up to 50% of surgeons treated a patient with a BRCA1/2 VUS the same as a patient with a pathogenic mutation. What is more, bilateral mastectomy rates range from 25-51% in patients with a VUS for BRCA1/2, which could represent overtreatment [13,18]. Given the increasing number of VUS results and variation in treatment patterns, we sought to evaluate the significance of a VUS genetic testing result on primary index breast cancer management.

MATERIAL AND METHODS

The study population was derived from the Inherited Care Registry (ICARE), which is an IRB-approved international database of volunteer subjects recruited from November 2000 to January 2017 interested in participating in studies about inherited cancer. Participants were recruited from the institutional genetics clinic, internal and external providers, and social media outlets and genetics conferences.

After consent was obtained, participants were mailed a comprehensive questionnaire which ascertained self reported demographic, clinical and family history. Within this questionnaire, knowledge about inherited cancer was assessed with a series of statements and the options for response were “TRUE”, “FALSE” or “DON’T KNOW”. Specific to this study, the statement “All individuals who have an altered inherited cancer gene get cancer” was chosen for analysis. The Cancer Worry Scale was also included in the questionnaire, for which the question “How worried are you about getting breast cancer someday?” was specifically chosen for analysis in this study. The options for response to the aforementioned question were” Not at all”, “Rarely”, “Sometimes”, “Often”, “Almost all the time”. All patient responses were coded into a secured database.

All participants within the ICARE database with a documented variant of unknown significance for 1 or more of the 11 high and moderate penetrant genes for breast cancer per the 2017 NCCN guidelines were identified. Participants who had a documented concurrent deleterious mutation for any gene were then excluded. Participants with a reported history of breast cancer were selected for analysis. Self-reported demographic, clinical and questionnaire variables were collected. Results were reported as frequencies for the categorical variables and medians (ranges) for continuous variables. Comparisons between groups were performed using either the Chi-square test or Fisher’s Exact test for categorical variables and the non-parametric Kruskal-Wallis test for continuous variables. A separate analysis was performed excluding patients who had surgery before 1996, prior to when genetic testing was commercially available, to adjust for any potential differences between groups. Ultimately, these patients were included in the final analysis, as their exclusion did not change the results. All analyses were performed in SAS version 9.4. Tests are deemed significant at the 0.05 significance level (and no corrections were made for multiple testing).

RESULTS

From the 2,252 participants in the ICARE registry, 1,568 participants with a VUS were identified. After excluding participants with a concurrent deleterious mutation, 181 (8%) participants with only a VUS remained. Of the 181 participants, 84 (46%) had a personal history of breast cancer and comprise our study cohort. Self-reported data was available for 79/84 subjects (94% response rate). The cohort was 100% female, 70% white, and 77% had some college education or higher (Table 1).

Table 1: Demographic and Clinical Characteristics of Patients with breast cancer + VUS, (n=79).

Median age at cancer diagnosis, years (range) 49(27-78)
Median age at VUS diagnosis, years (range) 59(31-79)
Median age at questionnaire, years (range) 59(32-82)
Gene with VUS, n (%)  
ATM 16 (20%)
BRCA1 16 (20%)
BRCA2 16 (20%)
BRCA NOS 1(1%)
CDH1 3(4%)
CHEK2 9(11%)
NBN 2(3%)
NF1 3(4%)
PALB2 8(10%)
PTEN 3(4%)
STK11 1(1%)
TP53 1(1%)
Female gender, n (%) 79(100%)
Ethnicity, n (%)  
White 55(70%)
Hispanic 5(6%)
Black 12(15%)
Asian 4(5%)
Other 3(4%)
Marital Status, n (%)  
Married 38
Single 8
Divorced 7
Widowed 23
Cohabitating 3
Some College Education or Higher, n (%)  
Yes 61
No 18
Personal History of cancer excluding ovarian cancer, n (%) 12
Personal History of Ovarian cancer, n (%) 2
First Degree relative with breast cancer n (%) 27
Bilateral Breast Cancer, n (%) 15
Menopausal Status, n (%)  
Premenopausal 26
Postmenopausal 51
Unknown 2
Surgical Management, n (%)  
Lumpectomy 35 (44%)
Mastectomy 15 (19%)
Bilateral Mastectomy 29 (37%)
Received Genetic Counseling, n (%)  
Yes 68 (86%)
No 3 (4%)
Unknown 8 (10%)
Genetic Testing Timing, n (%)  
Pre-operative 16 (20%)
Post-operative 63 (80%)
VUS = Variant of Unknown Significance  

All participants were from the United States, except one participant from the Bahamas. Median age of breast cancer diagnosis was 49, while median age of being diagnosed with a VUS was 59. A VUS of ATM, BRCA1 and BRCA2 were the most frequent. Initial surgical cancer management was as follows: 35 (44%) lumpectomies, 15 (19%) unilateral mastectomies and 29 (37%) bilateral mastectomies. In our cohort, there were 15 (19%) participants with bilateral breast cancer at diagnosis which were excluded from further analyses. Of note, 21/79 (27%) of participants self-reported a second cancer occurrence; the questionnaire responses were not able to classify whether a second occurrence represented a second primary tumor, a recurrent lesion, or a metastatic lesion.

There were 50 (78%) participants who received genetic testing results post-operatively. The median time of postoperative genetic testing was 3 years (range: 0-33 years). Among the postoperative genetic testing group, 16 (32%) had a therapeutic mastectomy plus contralateral prophylactic mastectomy (TM + CPM), 9 (18%) had a unilateral mastectomy and 25 (50%) had a lumpectomy (Figure 1).

Surgical Distribution (%) by Timing of Genetic Testing. The breakdown of surgical management by genetic testing pre- or post-operatively. There was no significant difference in surgery type by timing of genetic testing (p=0.520). (TM + CPM = Therapeutic Mastectomy + Contralateral Prophylactic Mastectomy)

Figure 1: Surgical Distribution (%) by Timing of Genetic Testing. The breakdown of surgical management by genetic testing pre- or post-operatively. There was no significant difference in surgery type by timing of genetic testing (p=0.520). (TM + CPM = Therapeutic Mastectomy + Contralateral Prophylactic Mastectomy)

Of the initial lumpectomy participants, 5/25 (20%) had an in-breast recurrence and opted for therapeutic mastectomy + contralateral prophylactic mastectomy. Of these participants, 3/5 (60%) had genetic testing prior to their conversion to bilateral mastectomy. One mastectomy participant opted for a contralateral prophylactic mastectomy after delayed genetic testing.

There were 14 (22%) participants who received genetic testing results pre-operatively, of which 7 (50%) had a TM + CPM, 2 (14%) had unilateral mastectomy, and 5 (36%) had a lumpectomy.

There were no significant differences between participants who had genetic testing pre- or post-operatively for age at diagnosis of breast cancer, ethnicity, marital status, education level, personal history of ovarian or other cancer, or first degree relative with breast cancer (Table 2).

Table 2: Comparison of Pre - and Post-Operative Genetic Testing Groups (Excluding Bilateral Breast Cancer) n=64.

  Post-Operative Pre-Operative Genetic  
  Genetic Testing Testing  
  n=50 n=14  
      p- value*
Median age at cancer diagnosis, years (range) 50 (27-73) 45(39-78) 0.51
Median age at VUS diagnosis, years (range) 60 (31-79) 46(40-79) 0.013
Menopausal Status, n (%)     0.048
Premenopausal 14 (29%)    
Postmenopausal 35(71%) 6 (43%)  
Ethnicity, n (%)     0.313
White 34(68%) 7 (50%)  
Hispanic 4(8%) 1 (7%)  
Black 8\(16%) 3 (21%)  
Asian 3(6%) 1 (7%)  
Other 1(2%) 2 (14%)  
Marital Status, n (%)     0.679
Married 25(50%) 7 (50%)  
Single 4(8%) 3 (21%)  
Divorced 4(8%) 1 (7%)  
Widowed 15(30%) 3 (21%)  
Cohabitating 2(4%) -  
Some College Education or Higher, n (%) 38(76%) 11 (79%) 1
Personal History of cancer excluding Ovarian cancer, n (%) 8 (16%) - 0.183
Personal History of Ovarian cancer, n (%) 2 (4%) - 1
First Degree relative with breast cancer n (%) 19 (38%) 4 (29%) 0.754
Surgical Management, n (%)     0.52
Lumpectomy 25 (50%) 5 (36%)  
Mastectomy 9 (18%) 2 (14%)  
TM + CPM 16 (32%) 7 (50%)  
Received Genetic Counseling, n (%) 46 (100%) 10 (83%) 0.04
Answered FALSE to “All individuals who have an altered inherited cancer gene get cancer”, n (%) 37 (74%) 7 (50%) 0.115
*For categorical variables, either the Chi-Square test or Fisher’s exact test was used, as appropriate. For the continuous variables, the Kruskal-Wallis test was used. TM + CPM = Therapeutic Mastectomy + Contralateral Prophylactic Mastectomy. Abbreviations: TM + CPM: Therapeutic Mastectomy + Contralateral Prophylactic Mastectomy

However, the median age at which participants were diagnosed with a VUS was significantly younger for those who had testing pre-operatively compared to those who had testing post-operatively (46 vs 60 years, p=0.013).

Participants who had genetic testing post-operatively were more likely to be postmenopausal at breast cancer diagnosis (71% vs 43%, p=0.048). When comparing only participants that underwent TM + CPM by timing of genetic testing (pre-operatively vs post-operatively), participants who had genetic testing postoperatively were more likely to be post-menopausal at breast cancer diagnosis as well (29% v 88%, p=0.01). When evaluating participants who had genetic testing pre-operatively by surgery type (lumpectomy/ unilateral mastectomy vs TM +CPM), there were no significant differences for age at diagnosis of breast cancer, age at VUS diagnosis, menopausal status, ethnicity, marital status, education level, personal history of ovarian or other cancer, or first degree relative with breast cancer.

A total of 56 (88%) of participants, reported having genetic counseling. Participants who had genetic testing post-operatively were more likely to have received genetic counseling (100% vs 83%, p=0.040). Forty-four (72%) participants answered “FALSE” to “All individuals who have an altered inherited cancer gene get cancer”, regardless of having received counseling. Of all participants who ultimately had bilateral mastectomies at the time of questionnaire completion (n=39, 49%), they were significantly more likely to answer “not at all” or “rarely” worried about getting cancer (67% vs 33%, p=0.011).


 

DISCUSSION

An advantage to patients appropriately tested for a genetic mutation after breast cancer diagnosis is identifying those who will benefit from risk reducing surgery, such as CPM, as populationbased risk stratification is no longer applicable. However, one pitfall of genetic testing is when the results are not completely informative, as is the case with a VUS. Ultimately, patients may be more likely to act upon the diagnosis of a VUS when tested before surgery. These patients are more likely to be younger and pre-menopausal, as seen in our cohort who underwent testing pre-operatively. Based on NCCN guidelines for genetic risk evaluation, any patient with a personal diagnosis of cancer ≤ 50 years old (previously ≤ 45 years old) is recommended to undergo genetic testing [9]. This is the rationale for the aforesaid study findings, and these patients should continue testing prior to surgery when available.

With the knowledge of a VUS diagnosis pre-operatively, more participants chose TM + CPM compared to those who tested positive for a VUS post-operatively, however, this was not statistically significant (50% vs 32%, p=0.215). Although this knowledge did not statistically significantly influence TM + CPM rate, a larger proportion of participants in the pre-operative genetic testing group suggests an influence that falls within the range of bilateral mastectomy rates for VUS cancer patients in previously published reports. Welsh at el showed that patients with a BRCA VUS had a prophylactic mastectomy of 22%. Kurian et al., reported that for a white female, ≤ 50 years of age with private insurance and a VUS diagnosis had a 43-51% chance of undergoing bilateral mastectomy.

Genetic counseling is imperative in helping both patients and surgeons decipher the rapidly growing body of knowledge in the genetic testing era. Although not much is known about a VUS, counselors can use other factors in context to help a patient understand their risk for future cancers based on personal and family history that can in turn be used for surgical decision making. Participants in our cohort who had genetic testing pre operatively were less likely to have genetic counseling. Limited availability of certified genetic counselors and apprehension to delay definitive surgical management are often cited reason for this gap in counseling [19]. Interestingly, with the suggestive influence of a VUS in uptake of contralateral prophylactic mastectomy in this highly educated and counseled cohort, most patients were aware that not “All individuals who have an altered inherited cancer gene get cancer”. One explanation for the aforementioned is participants might have felt that statement did not personally apply after already being diagnosed with cancer.

Studies have shown a higher distress rate in BRCA VUS patients compared to negative or pathogenic variants [13]. In our cohort, participants who ultimately had bilateral mastectomies at the time of completing the study questionnaire were significantly less concerned about getting cancer. Although this represents mood after final treatments for cancer, it suggests that fear of future cancer may be one of the driving forces of choosing bilateral mastectomy.

There are some limitations to this study that deserve mention. This is a retrospective study spanning 17 years based solely on self-reported data. Information from participants’ medical records, most importantly staging data, was not available for analysis. As a result, exact information regarding staging could not be used to evaluate surgical decision making ability other than in the context of a contralateral prophylactic mastectomy. The time frame of this dataset, which is a strength and limitation, predates commercially available genetic testing and risk stratification models. When adjusting for the year of surgery, this did not change the overall study findings. Even though the diagnosis of a VUS is increasing, it still represents a fairly small number of patients. As a result, our sample size may be too small to reflect a real difference in surgical decision making. Furthermore, the limited self-reported follow-up data regarding second cancer occurrences is insufficient to determine whether second cancer events affected further surgical decision making. Lastly, without case matched controls, no conclusions can be drawn regarding the self-reported second event rate of 27% being above reported recurrence rates in the general population.

Future directions include studying a larger cohort of VUS participants with longer follow-up data to include more clinical data like recurrences, if any. What is more, in follow-up surveys, inclusion of questions aimed at identifying specific reasons for bilateral mastectomy.

CONCLUSION

In this VUS cohort, a VUS was associated with a higher contralateral prophylactic mastectomy rate, though not statistically significant. Although it is not the only factor in surgical decision making, it is imperative that surgeons are aware that a VUS does not have data to support that it confers the same risk as a pathogenic mutation. In the setting of a VUS diagnosis, appropriateness for prophylactic surgery should not rely primarily on genetic testing results. Until further data is available to determine appropriateness of risk reducing strategies, patients with a VUS mutation should be treated as having a negative result and encouraged to join clinical trials to help determine the pathogenicity, if any, of their variant. Additionally, they should be followed in a registry or high-risk clinic to allow for follow-up on their personal and family health.

REFERENCES

1. PDQ® Cancer Genetics Editorial Board. PDQ Genetics of Breast and Gynecologic Cancers: Health Professional Version. Bethesda, MD: National Cancer Institute.

2. Agnese DM, Pollock RE. Breast Cancer Genetic Counseling: A Surgeon’s Perspective. Front Surg. 2016; 3: 1-7.

3. Hall J, Lee M, Newman B, Morrow J, Anderson L, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. 1990; 250: 1684-1689.

4. Narod SA, Feunteun J, Lynch HT, Watson P, Conway T, Lynch J, et al. Familial breast-ovarian cancer locus on chromosome 17q12-q23. Lancet (London, England). 1991; 338: 82-83.

5. Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994; 265: 2088-2090.

6. Statement of the American Society of Clinical Oncology: genetic testing for cancer susceptibility. Adopted on February 20, 1996. J Clin Oncol. 1996; 14: 1730-1736.

7. American Cancer Society. Breast Cancer Facts & Figures 2017-2018. Breast Cancer Facts & Figures. 2017.

8. Powers B, Pal T, Laronga C. Considerations in Testing for Inherited Breast Cancer Predisposition in the Era of Personalized Medicine. Surg Oncol Clin N Am. 2018; 27: 1-22.

9. Genetic/Familial High-Risk Assessment: Breast and Ovarian. NCCN Clinical Practice Guidelines in Oncology. 2018.

10. Robson ME, Storm CD, Weitzel J, Wollins DS, Offit K. American Society of Clinical Oncology Policy Statement update: Genetic and genomic testing for cancer susceptibility. J Clin Oncol. 2010; 28: 893-901.

11. Kurian AW, Hare EE, Mills MA, Kingham KE, McPherson L, Whittemore AS, et al. Clinical Evaluation of a Multiple-Gene Sequencing Panel for Hereditary Cancer Risk Assessment. J Clin Oncol. 2014; 32: 2001- 2009.

12. Culver J, Brinkerhoff C, Clague J, Yang K, Singh K, Sand S, et al. Variants of uncertain significance in BRCA testing: Evaluation of surgical decisions, risk perception, and cancer distress. Clin Genet. 2013; 84: 464-472.

13. Welsh JL, Hoskin TL, Day CN, Thomas AS, Cogswell JA, Couch FJ, et al. Clinical Decision-Making in Patients with Variant of Uncertain Significance in BRCA1 or BRCA2 Genes. Ann Surg Oncol. 2017; 24: 3067-3072.

14. Murray ML, Cerrato F, Bennett RL, Jarvik GP. Follow-up of carriers of BRCA1 and BRCA2 variants of unknown significance: variant reclassification and surgical decisions. Genet Med. 2011; 13: 998- 1005.

15. National Cancer Institute. Genetic Testing Fact Sheet - National Cancer Institute. 2018.

16. Tyrer J, Duffy SW, Cuzick J. A breast cancer prediction model incorporating familial and personal risk factors. Stat Med. 2004; 23: 1111-1130.

17. National Cancer Institute. Breast Cancer Risk Assessment Tool.

18. Kurian AW, Li Y, Hamilton AS, Ward KC, Hawley ST, Morrow M, et al. Gaps in Incorporating Germline Genetic Testing Into Treatment Decision-Making for Early-Stage Breast Cancer. J Clin Oncol. 2017; 35: 2232-2239.

19. Delikurt T, Williamson GR, Anastasiadou V, Skirton H. A systematic review of factors that act as barriers to patient referral to genetic services. Eur J Hum Genet. 2015; 23: 739-745.

Henry D, Lee M, Almanza D, Sun W, Boulware D, et al. (2018) Impact of Genetic Testing on Breast Cancer Surgery: Are the Variants Significant? JSM Genet Genomics 5(1): 1028

Received : 08 Nov 2018
Accepted : 01 Dec 2018
Published : 03 Dec 2018
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X