Synchronous and Metachronous Bilateral Breast Malignancies: Report of Two Cases and Literature Review

Introduction

Bilateral breast cancer (BBC) is a rare event accounting for 1%–3.2% of all breast malignancies. ¹ The second tumor in the contralateral breast is termed synchronous if it occurs within 6 months and as metachronous if later than that. The literature has conflicting evidence on the causation and management of these tumors. ² Metachronous bilateral breast cancer with a papillary carcinoma in the contralateral breast has rarely been reported in the literature.

Cases

Case 2

A 62-year-old female presented with a lump in her left breast that was associated with bleeding from the nipple. There was no history of weight loss, fever, or loss of appetite. Ultrasonography showed a complex, solid-cystic mass lesion with lobulated margins in the left breast. A mammography revealed a mass lesion in the retroareolar area of the left breast with ill-defined posterior margins along with many lymph nodes assessed as BIRADS category 4b. The right breast also had well-defined mass lesions in the upper and lower inner quadrants assessed as BIRADS category 3 (Fig. 1). The patient was diagnosed as having IDC, in each breast on the basis of tru-cut biopsies. Extensive ductal carcinoma in-situ was also noted on both sides.

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FIG. 1.

Mammogram showing a Breast Imaging Reporting and Data System (BIRADS) 4b lesion in the left breast and a BIRADS 3 lesion in the right breast (81 × 121 mm), in Case 2.

The tumor was negative for ER and PR, and positive for Her-2 neu. Following this, a modified radical mastectomy (modified BR Score 7, Grade 2) of the left breast and axillary clearance was performed and followed by chemotherapy. Of a total of 12 lymph nodes resected, 2 lymph nodes showed metastatic tumor deposits. The right breast was treated conservatively by lumpectomy followed by radiation therapy.

Discussion

The clinical significance and prognosis of BBC is still ambiguous and a matter of debate. The prevalence of synchronous breast carcinoma is ∼1%–3%, and the prevalence of metachronous breast carcinoma (MBC) is 5%–7%. The risk factors for BBC are variable, with heredity being the most significant one. Others factors include familial breast cancer, radiation exposure at young age, inadequate treatment received for the first tumor, nulliparity, lobular carcinoma in-situ, lobular invasive carcinoma, and multicentric cancer.^2,3 The trend in the occurrence of synchronous tumors, similar to unilateral breast cancer (UBC), in theory, involves an association with accumulated exposure to environmental carcinogens. In contrast, the high relative risk of metachronous contralateral breast cancer in young patients strongly suggests a genetic bias. Remarkably, BRCA mutations are more commonly seen in patients with metachronous cancers. ⁴

A study by Londero et al. reported that the prevalence of MBCs after 10 years from the original diagnosis was ∼40%. ⁵ The patient described under Case 1 presented with a metachronous papillary breast carcinoma in her right breast, 14 years after she was diagnosed with IDC of the left breast. Extended bilateral mammographies thus play a pivotal role in the postoperative follow-up of these patients. Annual breast ultrasonography is also used as an adjunct to mammography. Papillary carcinoma, a rare histologic variant of breast carcinoma, accounts for 0.5% of all newly diagnosed cases of breast cancer. This subtype has been reported to have better a outcome and prognosis, compared to IDC. ⁶ Development of a metachronous invasive papillary carcinoma of the breast has rarely been described. In a study of 113 patients of MBCs conducted by Senkus et al., only 2 cases of papillary carcinoma were reported. ⁴

The histopathologic characteristics and the biologic behavior of synchronous bilateral carcinoma (SBC) are still issues of debate. An SBC may represent either a second primary tumor or a metastasis from first tumor. ⁷ Numerous studies, including Chaudary et al., ⁸ have proposed guidelines to differentiate between a separate second primary and a metastasis to the other breast; comprising demonstration of in-situ component on either side, both carcinomas with different histologic types, and different grades of cancer with no evidence of local, regional, or distant metastasis. In the cases described in this article, both the left and the right breast carcinomas were accompanied by extensive in-situ components confirming the primary nature of these tumors. Mainly the absence of distant metastases increases the plausibility of contralateral breast tumors being separate primary tumors.^2,7,8 There is no clear relationship between ER and PR positivity and bilaterality of the tumors. However, BBC is more commonly seen in cases with Her-2 neu overexpression as present in the two cases described in this article. ²

The impact of developing an MBC or SBC on clinical outcome and prognosis is still not understood distinctly. Some studies suggest poor survival, while others report similar survival, compared to patients with UBC.^5,9 Most of the researchers agree that no significant difference exists in survival for patients with unilateral, compared to all bilateral, breast cancers. On the contrary, poorer survival in SBCs, compared to both MBCs and UBCs, has also been reported, and only a few studies describe an inverse tendency of better survival in cases of SBC, compared to MBC.^5,9

A similar scenario exists in the management of such patients with regard to surgical treatment options. A bilateral mastectomy rather than a breast-conserving intervention is mainly the preferred option, considering BBC's poor prognosis. However, there are reports confirming the efficacy of less-invasive management in BBC, as for unilateral tumors.^5,10,11

Conclusions

It has now been agreed that BBC is amenable to bilateral breast-conservation treatment without compromising survival and outcome.^5,7 A possible role for adjuvant hormonal therapies for halting the development of an eventual second primary breast carcinoma has also been suggested and is undergoing trials. A better understanding of the appropriate management options and their outcomes is still awaited, necessitating more studies in this area.