Case report of a patient with Neurofibromatosis type I and synchronous bilateral carcinoma breast

Purpose: Management of breast cancer in the setting of neurofibromatosis poses several challenges.

We report the case of a 45-year-old female with neurofibromatosis type 1, who presented with synchronous bilateral breast carcinoma and was treated with bilateral breast conservation surgery, adjuvant chemotherapy,radiation, and endocrine therapy.

Methodology: Our patient , a 45 year old female with NF- 1 presented with bilateral breast lumps.After a thorough clinical examination and bilateral mammogram evaluation , core biopsy obtained from bilateral breast lumps showed invasive carcinoma . A metastatic workup with CECT thorax, abdomen, and bone scan was done.
She underwent bilateral breast conservation surgery and sentinel node biopsy. Histopathology of the right breast lump showed invasive ductal carcinoma NST MBR grade II, pT1cN0 stage Ia. IHC was triple negative with Ki 67 - 40 %.Histopathology of the left breast lump was invasive carcinoma NST MBR Grade II ,with DCIS component.TNM stage was -pT2 N0 M0 - stage IIa.IHC showed ER + VE , PR + ve , Her 2 +ve with a Ki 67 of 30% .
Adjuvant dose-dense Adriamycin -60 mg/m2 (90 mg) and Cyclophosphamide -600 mg/m2 (900 mg )with pegfilgrastim support followed by dose-dense Paclitaxel 175 mg /m(260 mg ) and weekly Trastuzumab ( 4mg /kg followed by 2mg /kg weekly dose) was given.Adjuvant radiation was given to bilateral breasts using a rapid arc technique with simultaneous integrated boost, using a 6MV linear accelerator delivering 40 Gy in 15 fractions to bilateral breasts with a boost of 48 Gy in 15 fractions to lumpectomy sites bilaterally.Stringent dose constraints were achieved to avoid toxicities to nearby OARs. She is planned for continuation of 17 cycles of 3 weekly trastuzumab(6 mg /kg) and capecitabine maintenance therapy for 1 year at 650 mg/m2, followed by endocrine therapy with tamoxifen 20 mg OD for 10 years.

Results: We were faced with unique challenges.Difficulty in detecting a breast lump in the background of neurofibromas may have lead to a delay in diagnosis.In deciding upon the best surgical approach , due caution was taken ,since breast conservation therapy might pose an increased risk, of radiation-induced malignant transformation . While delivering radiation for bilateral breast cancer, the dose constraints to the heart and other critical organs had to be met. Moreover, neurofibromin depletion causes hypersensitivity to estradiol, thus explaining the poor prognosis associated with the use of Tamoxifen. Also, neurofibromin-deficient ER-positive breast cancer cells may develop resistance to selective estrogen receptor degraders (SERDs). In such cases, SERD/MEK inhibitor combinations are indicated to induce tumor regression.

Conclusions: In conclusion , breast carcinoma in the setting of NF-1 needs careful consideration of factors affecting diagnosis, surgical management , radiation delivery, endocrine therapy and follow up to improve survival outcomes.

References: