J Breast Cancer.  2019 Mar;22(1):131-140. 10.4048/jbc.2019.22.e10.

Whole Exome Sequencing in the Accurate Diagnosis of Bilateral Breast Cancer: a Case Study

• Li X
• Yang M
• Zhang Q
• Fan Y
• Zhu T
• Chen F
• Wang K

• KMID: 2441858
• DOI: http://doi.org/10.4048/jbc.2019.22.e10

Abstract

When faced with a case of bilateral breast cancer (BBC), understanding how to differentiate bilateral primary breast cancer from contralateral metastatic breast cancer is essential for treatment, but clear identification criteria have not been established to date. Diverse events play different roles in the therapy and prognosis of BBC; hence, it is of great significance to detect a more comprehensive and convincing technique to make an accurate differential diagnosis. We report a rare case of synchronous BBC in a 61-year-old Chinese woman. Based on her clinical and pathological features and the use of whole exome sequencing and cancer genome analysis, we concluded that the patient developed contralateral metastatic breast cancer which metastasized from left to right. Therefore, together with clinical, pathological and cancer genomics information, we could precisely define the origin and evolution of BBC.

Keyword

Breast neoplasms; Differential diagnosis; Neoplasm metastasis; Whole exome sequencing

MeSH Terms

Asian Continental Ancestry Group
Breast Neoplasms*
Breast*
Diagnosis*
Diagnosis, Differential
Exome*
Female
Genome
Genomics
Humans
Middle Aged
Neoplasm Metastasis
Prognosis

Figure

• 

  Figure 1 Imaging studies. (A) The 3 o'clock view of the areola area of the left breast; 1.0 cm away from the body surface, a hypoechoic mass of 1.2 × 0.6 cm with an irregular shape and unclear boundary can be seen. (B) The 12–3 o'clock view of the right breast; 0.7 cm away from the body surface, a hypoechoic mass of 4.4 × 2.4 cm with a “crab-feet” change and clear margin can be seen. (C) An abnormal signal is visible at the rear of the left nipple, about 1.7 × 0.9 cm in size. (D) The right breast has a large, abnormal signal mass, about 4.4 × 3.3 cm in size and lobulated, which is mainly distributed within the upper quadrant, and its edge has burrs. There is right nipple retraction, and the inner, upper quadrant of the skin is thickened. Mammograms of the mediolateral oblique (E, F) and AT (G, H) positions. Mammograms of the AT position show a hint of bilateral, lymphatic metastasis. AT = axillary tail.

• 

  Figure 2 Analysis of the biopsy tissues from the bilateral breast tumors. (A) The section on the left tumor showed an IDC, grade II (H & E × 250). (B-E) The left tumor revealed ER (95% 3+), PR (< 1% +), HER2 (1+), and Ki67 (30%) (IHC × 250). (F) The section on the right tumor showed an IDC, grade II (H & E × 250). (G-J) The right tumor revealed ER (50% 2+), PR (−), HER2 (−), Ki67 (30%) (IHC × 250). H & E = hematoxylin and eosin; IDC = invasive ductal carcinoma; IHC = immunohistochemistry; ER = estrogen receptor; PR = progesterone receptor; HER2 = human epidermal growth factor receptor 2.

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  Figure 3 Analysis of the biopsy tissues of the bilateral axillary LNs. (A) The LN of left axilla showed an IDC, grade II (H & E,× 250) (B-E) The LN of the left axilla revealed ER (60% 3+), PR (−), HER2 (1+), and Ki67 (30%) (IHC, × 250). (F) The LN of the right side showed an IDC, grade II (H & E, × 250). (G-J) The LN of the right axilla revealed ER (90% 3+), PR (< 1% +), HER2 (−), and Ki67 (25%) (IHC, × 250). LN = lymph node; H & E = hematoxylin and eosin; IHC = immunohistochemistry; IDC = invasive ductal carcinoma; ER = estrogen receptor; PR = progesterone receptor; HER2 = human epidermal growth factor receptor 2.

• 

  Figure 4 Analysis of whole exome sequencing research. (A) Mutation heatmap for the BBCs and axillary LNs. All L, LN, R samples share 9 common variations which are not found in RN. These variations are AK3, PIEZO1, OR8B3, WDR17, PLXNA1, PCYT1A, ZNF629, TRDMT1 and OR6B3. (B) VAF distribution (%) for the BBCs and axillary LNs. The mean VAF of those shared common variations are 5%, 15% and 16% in L, LN and R samples respectively. Yellow = a gene with a mutation; Blue = a gene without mutation; LN = lymph node; BBC = bilateral breast cancer; VAF = variation frequency.

• 

  Figure 5 CNVs of the BBCs. CNVs in the left breast tumor were similar to those in the right lesion. Chr8 and chr11 displayed a high gene-amplification pattern. CNV = copy number variation; BBC = bilateral breast cancer.

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  Figure 6 The CNV distribution of all chromosomes. Chr6/11/13 LOH were shown in the right breast cancer. CNV = copy number variation; LOH = loss of heterozygosity.

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