1Hereditary Cancer Clinic, Cancer Prevention Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
2Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea
3Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea
4Division of Nursing, Severance Hospital, Seoul, Korea
5Department of Obstetrics and Gynecology, Institute of Women’s Life Medical Science, Women’s Cancer Clinic, Yonsei University College of Medicine, Seoul, Korea
6Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea
7Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
8Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
Copyright © 2022 by the Korean Cancer Association
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ethical Statement
The ethical principles for medical research established by the World Medical Association Declaration of Helsinki were followed throughout the study. The institutional review board at Severance Hospital, Seoul, Korea reviewed and approved this study (IRB approval number: 4-2015-0819 and 4-2018-0259). We obtained informed consent from all patients who participated in this study.
Author Contributions
Conceived and designed the analysis: Park JS, Park HS.
Collected the data: Park JS, Shin S, Lee YJ, Lee ST, Nam EJ, Han JW, Lee SH, Kim TI, Park HS.
Contributed data or analysis tools: Park JS, Shin S, Lee YJ, Lee ST, Nam EJ, Han JW, Lee SH, Kim TI, Park HS.
Performed the analysis: Park JS, Shin S, Lee YJ, Lee ST, Park HS.
Wrote the paper: Park JS, Park HS.
Administration support: Park HS.
Conflicts of Interest
Conflict of interest relevant to this article was not reported.
Clinicopathological variable | PV/LPV (n=76) | VUS or ND (n=624) | p-value |
---|---|---|---|
Age at first diagnosis of breast cancer (yr) | 44 (25–82) | 43 (17–83) | 0.628 |
Sex | |||
Male | 2 (2.6) | 5 (0.8) | 0.171a) |
Female | 74 (97.4) | 619 (99.2) | |
Breast cancer, laterality | |||
Unilateral | 64 (84.2) | 554 (88.8) | 0.250a) |
Bilateral (metachronous) | 6 (7.9) | 24 (3.8) | |
Bilateral (synchronous) | 6 (7.9) | 46 (7.4) | |
Pathology | |||
IDC | 55 (72.4) | 435 (69.7) | 0.545a) |
ILC | 5 (6.6) | 18 (2.9) | |
DCIS | 11 (14.5) | 119 (19.1) | |
LCIS | 1 (1.3) | 10 (1.6) | |
Others | 4 (5.2) | 39 (6.3) | |
Unknown | 0 | 3 (0.5) | |
Hormone receptor | |||
Positive | 51 (67.1) | 156 (25.0) | 0.255a) |
Negative | 23 (30.3) | 460 (73.7) | |
Unknown | 2 (2.6) | 8 (1.3) | |
TNBC | |||
TNBC | 15 (19.7) | 98 (15.7) | 0.367 |
Others | 61 (80.3) | 526 (84.3) | |
Education | |||
University/College graduate | 43 (56.6) | 375 (60.1) | 0.301a) |
High school graduate | 24 (31.6) | 161 (25.8) | |
Middle graduate | 1 (1.3) | 26 (4.2) | |
No/Elementary school graduate | 3 (3.9) | 9 (1.5) | |
Unknown | 5 (6.6) | 53 (8.5) | |
Family history of breast cancer | |||
Yes | 30 (39.5) | 288 (46.2) | 0.269 |
No | 46 (60.5) | 336 (53.8) | |
Family history of ovarian cancer | |||
Yes | 7 (9.2) | 26 (4.2) | 0.076a) |
No | 69 (90.8) | 598 (95.8) | |
Second cancer history (multi-selection) | |||
Yes | 19 (25.0) | 86 (13.8) | 0.010 |
Thyroid | 9 (11.8) | 40 (6.4) | 0.080 |
Colorectal | 4 (5.3) | 10 (1.6) | 0.055a) |
Lung | 2 (2.6) | 4 (0.6) | 0.131a) |
Endometrium | 1 (1.3) | 6 (1.0) | 0.554a) |
Ovary | 2 (2.6) | 3 (0.6) | 0.131a) |
Pancreas | 0 | 2 (0.3) | > 0.99a) |
Sarcoma | 0 | 2 (0.3) | > 0.99a) |
Lymphoma | 0 | 2 (0.3) | > 0.99a) |
Leukemia | 0 | 1 (0.2) | > 0.99a) |
Kidney | 0 | 4 (0.6) | > 0.99a) |
Urothelial | 0 | 1 (0.2) | > 0.99a) |
Stomach | 0 | 12 (1.9) | 0.630a) |
Small bowel | 1 (1.3) | 1 (0.2) | 0.205a) |
Paraganglioma | 1 (1.3) | 0 | 0.109a) |
Liver | 0 | 3 (0.5) | > 0.99a) |
Uterine cervix | 4 (5.3) | 2 (0.3) | 0.002a) |
No | 57 (75.0) | 538 (86.2) | |
Experience of full-term delivery | |||
Yes | 63 (82.9) | 461 (73.9) | 0.087 |
No | 13 (17.1) | 163 (26.1) |
Values are presented as median (range) or number (%). DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LCIS, lobular carcinoma in situ; LPV, likely pathogenic variant; ND, not detected; PV, pathogenic variant; TNBC, triple negative breast cancer; VUS, variant of unknown significance.
a) These values were analyzed using Fisher exact tests.
AD, autosomal dominant; AoV, ampulla of Vater; Bil(met), bilateral breast cancer, metachronous; Bil(syn), bilateral breast cancer, synchronous; CRC, colorectal cancer; DCIS, ductal carcinoma in situ; ER, estrogen receptor; F, female; FS, frameshift; HER2, human epidermal growth factor receptor 2; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; Lt, left; MS, missense; NS, nonsense; Panc, pancreas; Pros, prostate; Rt, right; TNBC, triple negative breast cancer.
CI, confidence interval; N/A, not applicable; OR, odds ratio; TNBC, triple negative breast cancer.
a) Genes with inheritance of increased breast cancer risk according to the National Comprehensive Cancer Network, American Society of Clinical Oncology, or European Society of Medical Oncology guidelines: number of patients with mutation in each gene; ATM (10), BARD1 (1), BRIP1 (7), CHEK2 (2), NF1 (1), PALB2 (17), PTEN (1), RAD51D (7), TP53 (6).
Clinicopathological variable | PV/LPV (n=76) | VUS or ND (n=624) | p-value |
---|---|---|---|
Age at first diagnosis of breast cancer (yr) | 44 (25–82) | 43 (17–83) | 0.628 |
Sex | |||
Male | 2 (2.6) | 5 (0.8) | 0.171 |
Female | 74 (97.4) | 619 (99.2) | |
Breast cancer, laterality | |||
Unilateral | 64 (84.2) | 554 (88.8) | 0.250 |
Bilateral (metachronous) | 6 (7.9) | 24 (3.8) | |
Bilateral (synchronous) | 6 (7.9) | 46 (7.4) | |
Pathology | |||
IDC | 55 (72.4) | 435 (69.7) | 0.545 |
ILC | 5 (6.6) | 18 (2.9) | |
DCIS | 11 (14.5) | 119 (19.1) | |
LCIS | 1 (1.3) | 10 (1.6) | |
Others | 4 (5.2) | 39 (6.3) | |
Unknown | 0 | 3 (0.5) | |
Hormone receptor | |||
Positive | 51 (67.1) | 156 (25.0) | 0.255 |
Negative | 23 (30.3) | 460 (73.7) | |
Unknown | 2 (2.6) | 8 (1.3) | |
TNBC | |||
TNBC | 15 (19.7) | 98 (15.7) | 0.367 |
Others | 61 (80.3) | 526 (84.3) | |
Education | |||
University/College graduate | 43 (56.6) | 375 (60.1) | 0.301 |
High school graduate | 24 (31.6) | 161 (25.8) | |
Middle graduate | 1 (1.3) | 26 (4.2) | |
No/Elementary school graduate | 3 (3.9) | 9 (1.5) | |
Unknown | 5 (6.6) | 53 (8.5) | |
Family history of breast cancer | |||
Yes | 30 (39.5) | 288 (46.2) | 0.269 |
No | 46 (60.5) | 336 (53.8) | |
Family history of ovarian cancer | |||
Yes | 7 (9.2) | 26 (4.2) | 0.076 |
No | 69 (90.8) | 598 (95.8) | |
Second cancer history (multi-selection) | |||
Yes | 19 (25.0) | 86 (13.8) | 0.010 |
Thyroid | 9 (11.8) | 40 (6.4) | 0.080 |
Colorectal | 4 (5.3) | 10 (1.6) | 0.055 |
Lung | 2 (2.6) | 4 (0.6) | 0.131 |
Endometrium | 1 (1.3) | 6 (1.0) | 0.554 |
Ovary | 2 (2.6) | 3 (0.6) | 0.131 |
Pancreas | 0 | 2 (0.3) | > 0.99 |
Sarcoma | 0 | 2 (0.3) | > 0.99 |
Lymphoma | 0 | 2 (0.3) | > 0.99 |
Leukemia | 0 | 1 (0.2) | > 0.99 |
Kidney | 0 | 4 (0.6) | > 0.99 |
Urothelial | 0 | 1 (0.2) | > 0.99 |
Stomach | 0 | 12 (1.9) | 0.630 |
Small bowel | 1 (1.3) | 1 (0.2) | 0.205 |
Paraganglioma | 1 (1.3) | 0 | 0.109 |
Liver | 0 | 3 (0.5) | > 0.99 |
Uterine cervix | 4 (5.3) | 2 (0.3) | 0.002 |
No | 57 (75.0) | 538 (86.2) | |
Experience of full-term delivery | |||
Yes | 63 (82.9) | 461 (73.9) | 0.087 |
No | 13 (17.1) | 163 (26.1) |
Values are presented as median (range) or number (%). DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LCIS, lobular carcinoma in situ; LPV, likely pathogenic variant; ND, not detected; PV, pathogenic variant; TNBC, triple negative breast cancer; VUS, variant of unknown significance.
a)These values were analyzed using Fisher exact tests.
Case | Sex | Age at first diagnosis of breast cancer (yr) | Breast cancer Side/Path (subtype) | Family history kind (degree*n) | Second cancer | Affected genes | Nucleotide change | Amino acid change | Effect | Mode of inheritance | Zygosity | dbSNP |
---|---|---|---|---|---|---|---|---|---|---|---|---|
P027 | F | 34 | Rt/IDC (TNBC) | CRC (2*1) | - | PALB2 | c.1381C>G | p.Gln461Glu | MS | AD | Hetero | - |
P030 | F | 38 | Lt/ILC (ER+/HER2−) | Breast (1*1), Lung (1*1) | - | PALB2 | c.1426delA | p.Arg476Glufs | FS | AD | Hetero | - |
P041 | F | 50 | Lt/DCIS (ER+/HER2−) | Breast (1*1), Lung (1*1) | - | PALB2 | c.1426delA | p.Arg476Glufs | FS | AD | Hetero | - |
P032 | F | 38 | Lt/LCIS (ER+/HER2−) | Breast (2*2) | - | PALB2 | c.1516C>T | p.Gln506Ter | NS | AD | Hetero | - |
P036 | F | 47 | Rt/IDC (ER+/HER2−) | Breast (1*1), Stomach (1*2) | AoV | PALB2 | c.2257C>T | p.Arg753Ter | NS | AD | Hetero | - |
P042 | F | 54 | Lt/IDC (ER+/HER2−) | Breast (1*1), Kidney (1*1), Esophagus (1*1) | - | PALB2 | c.228_229delAT | p.Ile76Metfs | FS | AD | Hetero | - |
P048 | F | 44 | Rt/DCIS (ER+/HER2−) | Stomach (2*1) | Ovary | PALB2 | c.355C>T | p.Gln119Ter | NS | AD | Hetero | - |
P005 | F | 28 | Rt/DCIS (ER+/HER2−) | Stomach (2*1), Pros (2*1), Liver (2*1) | - | PALB2 | c.2406_2407delTG | p.Cys802Ter | NS | AD | Hetero | - |
P040 | F | 52 | Lt/IDC (ER+/HER2−) | Stomach (1*1), Skin (1*1) | Cervix | PALB2 | c.2485C>T | p.Gln829Ter | NS | AD | Hetero | - |
P014 | F | 25 | Lt/Medullary (TNBC) | Breast (2*2), CRC (2*2) | - | PALB2 | c.2748+1G>A | - | Splicing | AD | Hetero | rs753153576 |
P049 | F | 62 | Lt/IDC (TNBC) | Breast (1*1), Stomach (1*2) | - | PALB2 | c.2748+1G>A | - | Splicing | AD | Hetero | rs753153576 |
P063 | F | 45 | Rt/ILC (ER+/HER2−) | Breast (2*1, 3*1) | - | PALB2 | c.3256C>T | p.Arg1086Ter | NS | AD | Hetero | rs587776527 |
P101 | F | 60 | Lt/IDC (ER+/HER2−) | Ovary (1*1) | - | PALB2 | c.3350+5G>A | - | Splicing | AD | Hetero | rs587782566 |
P102 | F | 38 | Bil(syn)/IDC (ER+/HER2+) | Ovary (1*1) | - | PALB2 | c.3350+5G>A | - | Splicing | AD | Hetero | rs587782566 |
P010 | F | 50 | Rt/IDC (ER+/HER2−) | Breast (1*1), Stomach (1*1), Panc (2*1), Sarcoma (1*1) | - | PALB2 | Exon 1_11 deletion | - | Exon deletion | AD | Hetero | - |
P011 | F | 47 | Bil(met)/IDC (TNBC) | Breast (1*2) | - | PALB2 | Exon 11 deletion | - | Exon deletion | AD | Hetero | - |
P059 | F | 47 | Rt/IDC (TNBC) | Breast (2*2), CRC (1*1, 2*1), cervix | - | PALB2 | Exon 8 deletion | - | Exon deletion | AD | Hetero | - |
P070 | F | 47 | Lt/mucinous (ER+/HER2−) | Breast (2*1), Lung (2*1), Leukemia (2*1) | - | TP53 | c.542G>A | p.Arg181His | MS | AD | Hetero | rs397514495 |
P023 | F | 51 | Lt/IDC (ER+/HER2−) | Breast (1*2), Ovary (1*1) | - | TP53 | c.542G>A | p.Arg181His | MS | AD | Hetero | rs397514495 |
P006 | F | 41 | Bil(met)/DCIS (ER−/HER2+) | 0 | Lung, melanoma, sarcoma | TP53 | c.646G>A | p.Val216Met | MS | AD | Hetero | rs730882025 |
P034 | F | 32 | Bil(syn)/IDC (ER−/HER2+) | Stomach (1*1), Panc (1*1) | - | TP53 | c.733G>A | p.Gly245Ser | MS | AD | Hetero | rs28934575 |
P025 | F | 38 | Rt/DCIS (unknown) | 0 | - | TP53 | c.743G>A | p.Arg248Gln | MS | AD | Hetero | rs11540652 |
P021 | F | 30 | Rt/IDC (ER+/HER2+) | Stomach (2*2), Lung (2*1), Liver (2*1), Lymphoma (2*1) | - | TP53 | c.824G>A | p.Cys275Tyr | MS | AD | Hetero | - |
P062 | F | 37 | Bil(syn)/IDC (ER+/HER2−) | Thyroid (1*1) | - | PTEN | c.813_815delinsCC | p.His272Profs | FS | AD | Hetero | - |
AD, autosomal dominant; AoV, ampulla of Vater; Bil(met), bilateral breast cancer, metachronous; Bil(syn), bilateral breast cancer, synchronous; CRC, colorectal cancer; DCIS, ductal carcinoma in situ; ER, estrogen receptor; F, female; FS, frameshift; HER2, human epidermal growth factor receptor 2; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; Lt, left; MS, missense; NS, nonsense; Panc, pancreas; Pros, prostate; Rt, right; TNBC, triple negative breast cancer.
Clinicopathological risk factor | Mutation (n=52) | Vs. not detected (n=89) | |||||
---|---|---|---|---|---|---|---|
| |||||||
Simple regression | Multiple regression | ||||||
|
| ||||||
OR | 95% CI | p-value | OR | 95% CI | p-value | ||
Age at first diagnosis of breast cancer ≤ 40 yr | 21 | 0.758 | 0.379–1.516 | 0.433 | - | - | - |
| |||||||
Male breast cancer | 0 | N/A | - | - | N/A | - | - |
| |||||||
Bilateral breast cancer | 10 | 5.060 | 1.498–17.087 | 0.009 | 5.619 | 1.623–19.455 | 0.006 |
| |||||||
TNBC | 10 | 1.175 | 0.485–2.847 | 0.722 | - | - | - |
| |||||||
Family history of breast cancer | 23 | 0.741 | 0.373–1.474 | 0.393 | - | - | - |
| |||||||
Family history of ovarian cancer | 5 | 4.628 | 0.864–24.775 | 0.073 | 5.470 | 0.980–30.545 | 0.053 |
| |||||||
Presence of other primary cancer | 10 | 2.116 | 0.798–5.610 | 0.132 | 2.665 | 0.977–7.267 | 0.055 |
CI, confidence interval; N/A, not applicable; OR, odds ratio; TNBC, triple negative breast cancer.
a)Genes with inheritance of increased breast cancer risk according to the National Comprehensive Cancer Network, American Society of Clinical Oncology, or European Society of Medical Oncology guidelines: number of patients with mutation in each gene; ATM (10), BARD1 (1), BRIP1 (7), CHEK2 (2), NF1 (1), PALB2 (17), PTEN (1), RAD51D (7), TP53 (6).
Pre-test | Post-test | p-value | |
---|---|---|---|
Concern about the possibility of cancer in the future | 4.21±0.883 | 3.94±1.048 | < 0.001 |
Influence on mood | 3.27±0.645 | 3.13±0.694 | < 0.001 |
Influence on daily functioning | 3.03±0.758 | 2.94±0.729 | 0.006 |
Knowledge about hereditary cancer (max. point 100) | 66.9±21.7 | 68.8±21.8 | 0.025 |
Values are presented as average±standard deviation.
Concern about the possibility of breast cancer in the future | Influence on mood | Influence on daily functioning | |||||||
---|---|---|---|---|---|---|---|---|---|
|
|
| |||||||
B | 95% CI | p-value | B | 95% CI | p-value | B | 95% CI | p-value | |
Age ≤ 40 yr | 0.255 | 0.042 to 0.467 | 0.019 | 0.150 | 0.009 to 0.291 | 0.037 | 0.173 | 0.025 to 0.321 | 0.022 |
| |||||||||
Bilateral breast cancer | −0.391 | −0.716 to −0.065 | 0.019 | −0.146 | −0.363 to 0.071 | 0.187 | −0.079 | −0.307 to 0.150 | 0.498 |
| |||||||||
TNBC | 0.283 | −0.005 to 0.570 | 0.054 | 0.140 | −0.050 to 0.331 | 0.149 | 0.214 | 0.014 to 0.414 | 0.036 |
| |||||||||
Family history of breast or ovarian cancer | −0.052 | −0.266 to 0.161 | 0.630 | 0.031 | −0.110 to 0.172 | 0.666 | −0.016 | −0.164 to 0.133 | 0.837 |
| |||||||||
Highly educated (above college graduates) | 0.002 | −0.002 to 0.006 | 0.388 | 0.0005 | −0.002 to 0.003 | 0.724 | 0.0003 | −0.002 to 0.003 | 0.816 |
| |||||||||
PV/LPV detected | 0.503 | 0.140 to 0.866 | 0.007 | 0.142 | −0.100 to 0.384 | 0.250 | 0.102 | −0.152 to 0.357 | 0.477 |
| |||||||||
Counselee’s satisfaction to genetic test with counseling | −0.176 | −0.333 to −0.019 | 0.028 | −0.125 | −0.229 to −0.021 | 0.018 | −0.134 | −0.243 to −0.025 | 0.016 |
| |||||||||
Stage IV breast cancer | 0.396 | −0.453 to 1.244 | 0.360 | 0.547 | −0.013 to 1.107 | 0.055 | 0.235 | −0.356 to 0.825 | 0.435 |
| |||||||||
Genetic knowledge (post-test) | 0.339 | −0.150 to 0.829 | 0.174 | 0.049 | −0.276 to 0.375 | 0.765 | 0.136 | −0.206 to 0.477 | 0.435 |
B, beta regression coefficient value; CI, confidence interval; LPV, likely pathogenic variant; PV, pathogenic variant; TNBC, triple negative breast cancer.
Concern about the possibility of breast cancer in the future | Influence on mood | Influence on daily functioning | |||||||
---|---|---|---|---|---|---|---|---|---|
|
|
| |||||||
B | 95% CI | p-value | B | 95% CI | p-value | B | 95% CI | p-value | |
Age ≤ 40 yr | 0.201 | 0.015 to 0.417 | 0.068 | 0.149 | 0.009 to 0.288 | 0.037 | 0.173 | 0.018 to 0.312 | 0.027 |
| |||||||||
Bilateral breast cancer | −0.292 | −0.624 to −0.040 | 0.085 | - | - | - | - | - | - |
| |||||||||
TNBC | 0.196 | −0.090 to 0.481 | 0.179 | - | - | - | 0.181 | −0.018 to 0.379 | 0.075 |
| |||||||||
PV/LPV detected | 0.427 | 0.057 to 0.797 | 0.024 | - | - | - | - | - | - |
| |||||||||
Counselee’s satisfaction to genetic test with counseling | −0.117 | −0.276 to 0.043 | 0.152 | −0.125 | −0.228 to −0.022 | 0.018 | −0.125 | −0.234 to −0.017 | 0.024 |
| |||||||||
Stage IV breast cancer | - | - | - | 0.535 | −0.019 to 1.089 | 0.058 | - | - | - |
B, beta regression coefficient value; CI, confidence interval; LPV, likely pathogenic variant; PV, pathogenic variant; TNBC, triple negative breast cancer.
Values are presented as median (range) or number (%). DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; LCIS, lobular carcinoma These values were analyzed using Fisher exact tests.
AD, autosomal dominant; AoV, ampulla of Vater; Bil(met), bilateral breast cancer, metachronous; Bil(syn), bilateral breast cancer, synchronous; CRC, colorectal cancer; DCIS, ductal carcinoma in situ; ER, estrogen receptor; F, female; FS, frameshift; HER2, human epidermal growth factor receptor 2; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; Lt, left; MS, missense; NS, nonsense; Panc, pancreas; Pros, prostate; Rt, right; TNBC, triple negative breast cancer.
CI, confidence interval; N/A, not applicable; OR, odds ratio; TNBC, triple negative breast cancer. Genes with inheritance of increased breast cancer risk according to the National Comprehensive Cancer Network, American Society of Clinical Oncology, or European Society of Medical Oncology guidelines: number of patients with mutation in each gene;
Values are presented as average±standard deviation.
B, beta regression coefficient value; CI, confidence interval; LPV, likely pathogenic variant; PV, pathogenic variant; TNBC, triple negative breast cancer.
B, beta regression coefficient value; CI, confidence interval; LPV, likely pathogenic variant; PV, pathogenic variant; TNBC, triple negative breast cancer.