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Case presentation ceptor [ER] positive, progesterone receptor [PR] positive

JOURNAL OF MEDICALCASE REPORTS

Khalil et al. Journal of Medical Case Reports (2015) 9:61 DOI 10.1186/s13256-015-0533-8She was started on adjuvant tamoxifen (20mg, orally)immediately after radiation and was asked to continue

* Correspondence: Jihane.khalil@gmail.com; afifmed@hotmail.comRadiation Therapy Department, National Cancer Institute, Rabat, MoroccoCase oneA 39-year-old white Arabic woman was referred to ourcenter for adjuvant radiotherapy of a ductal carcinomain her right breast. She was diagnosed with NF1 by herneurologist when she was eight years old; she was notedto have several cafe-au-lait spots (Figure 1).

and human epidermal growth factor [HER] 2 positive).She received adjuvant chemotherapy (three courses ofFEC (cyclophosphamide, epirubicin and 5-fluorouracil)followed by three courses of docetaxel with trastuzumab(Herceptin) three weeks after her surgery. Radiotherapywas delivered to her chest wall and regional nodes to atotal dose of 42Gy after completion of chemotherapy.ease that mainly affects the skin and the nervous system.It is an autosomal dominant disorder that affects 1 in3000 individuals [1] and is characterized by cafe-au-laitspots and multiple neurofibromas. NF1 has beenreported to be associated with various types of cancers,especially tumors derived from the embryogenic neuralcrest, including pheochromocytoma, leukemia, glioma,rhabdomyosarcoma, astrocytoma and neurofibrosarcoma[2,3]. Breast cancer is rarely reported in association withNF1. We report the cases of three white Arabic womenpresenting with breast cancer and a previous diagnosisof NF1, and review the available data in the literature.

was noted to be hard and irregular. A mammographywas then performed and suggested the malignancy ofthe lesion, as it was staged as stage 4 according to theBreast Imaging Reporting and Data System (BI-RADS)established by the American College of Radiology(ACR). Her biopsy was positive for invasive ductal car-cinoma and her additional work-up was negative for dis-tant metastasis via bone scan, chest and abdominalcomputed tomography (CT).A mastectomy, along with a right axillary lymph node

dissection, were performed and the tumor was classifiedas stage PT3N2M0(IIIA) according to the TNM StagingSystem for Breast Cancer adopted by the American JointCommittee on Cancer (AJCC), (luminal B, estrogen re-Introduction: Neurofibromatosis type 1, also known as Vdisease that mainly affects the skin and the nervous systerisk of developing various types of cancers, especially tumits association with breast cancer has seldom been report

Case presentation: We report the cases of three white Awith a median age of 40-years-old (range: 39 to 43), who

Conclusions: The association between neurofibromatosiswe readdress this association through a literature review.

Keywords: Neurofibromatosis, Breast cancer, Uncommon

IntroductionNeurofibromatosis type 1 (NF1), also known as VonRecklinghausens disease, is a rare neuroectodermal dis-Breast cancer associatedtype 1: a case series andJihane Khalil*, Mohamed Afif*, Hanan Elkacemi, Meryem B 2015 Khalil et al.; licensee BioMed Central. TCommons Attribution License (http://creativecreproduction in any medium, provided the orDedication waiver (http://creativecommons.orunless otherwise stated.Open Access

ith neurofibromatosiseview of the literaturenoulaid, Tayeb Kebdani and Noureddine Benjaafar

Recklinghausens disease, is a rare neuroectodermal. Patients with neurofibromatosis type 1 have a highers derived from the embryogenic neural crest. However,.

bic women diagnosed with neurofibromatosis type 1,ught treatment at our centre for breast cancer.

pe 1 and breast cancer is uncommon. In our case series

ssociation

She had presented with a large lump in the superiorouter quadrant of her right breast one year before heradmission to our department. On palpation, this lumphis is an Open Access article distributed under the terms of the Creativeommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andiginal work is properly credited. The Creative Commons Public Domaing/publicdomain/zero/1.0/) applies to the data made available in this article,

Figure 1 Case one: photograph of caf-au-lait spots.

Khalil et al. Journal of Medical Case Reports (2015) 9:61 Page 2 of 4this treatment for five years. After 28 months, she re-mains well with no signs of recurrence of her breastcancer.

Case twoA white Arabic 40-year-old woman presented to ourcenter with cancer of her left breast. She was diagnosedas having NF1 at seven years of age; she had the classicalform of neurofibromatosis, with multiple nerofibromasover her limbs and trunk (Figure 2).Figure 2 Case two: photograph of neurofibromas in the trunkand the limbs after mastectomy.With no family history of breast cancer, she was diag-nosed at 40-years-old with cancer of her left breast. Hermammography showed an irregular 8cm lump in theretro-areolar area, classified as stage ACR5. A biopsy ofthe lesion confirmed its malignancy, and the histologicaltype was invasive ductal carcinoma.After the weekly team board meeting, a radical mast-

ectomy with homolateral axillary nodes dissection wasrecommended. Her tumor was classified as stagePT3N3M0 (IIIC), according to the pathologic findings,and it was a triple negative. An adjuvant chemotherapyand radiotherapy was delivered. She received three cy-cles of anthracycline followed by three cycles of doce-taxel. Radiation therapy was delivered to her left chestwall along with regional lymph nodes to a total dose of42Gy. At 30 months after her mastectomy she exhibitsno evidence of recurrence.

Case threeWe present the case of a 43-year-old white Arabicwoman whose diagnosis of NF1 was made soon afterbirth, when she was noted to have numerous cafe-au-laitspots and progressively developed axillary lentigines andneurofibromatous lesions on her trunk and limbs. At 43years old she noted a mobile lump in her upper internalleft breast quadrant upon self-examination. A biopsywas taken and tested positive for invasive ductal carcin-oma. She received the same treatment as patients incases one and two as her tumor was also classified asstage PT3N2M0 (IIIA). Adjuvant systemic hormonaltherapy was prescribed for five years as she was ER andPR positive. At two years after her mastectomy she re-mains free of any local recurrence or distal metastasis.

DiscussionNF1 is a complex neuroectodermal disorder character-ized by its autosomal dominant inheritance, high pene-trance and a wide variability in expression. The NF1gene is located in the peri-centromeric region of thelong arm of chromosome 17 (which also houses theBRCA1 gene). It regulates the conversion of the activeRas-GTP to inactive Ras-GDP. Ras is known as an es-sential component of signal transduction pathways thatregulate growth, proliferation, differentiation, and apop-tosis. The conversion from the GTP- to the GDP-boundform is mediated by the intrinsic GTPase activity of Ras.The impairment of this hydrolytic reaction is associatedwith an increased risk of cancer [3]. Hence, it has apotential role as a tumor suppressor gene [4]. The asso-ciation between NF1 and malignant tumors has beenwidely described; the most common reported associa-tions are with gliomas, malignant peripheral nerve

sheath tumors (MPNST), leukemia and rhabdomyosar-coma [2,3]. Concerning the association between NF1

and breast cancer, only a few cases have been reported[5,6]. Interestingly, about 28% of sporadic breast cancersare missing at least one copy of the NF1 gene, either dueto deletion or mutation [7].Clinically, NF1 is recognized mostly by multiple

neurofibromas, caf-au-lait spots and Lisch nodules[2,3]. The National Institutes of Health in the UnitedStates defined seven eligible criteria by which to diag-nose NF1; the diagnosis of NF1 is established when-ever two signs are associated in the same individual(Table 1) [8].The first cases describing the association of NF1 with

breast cancer were reported in the 1970s by Brasfield

Khalil et al. Journal of Medical Case Reports (2015) 9:61 Page 3 of 4and Das Gupta. They described their experience withfive patients, including one who had bilateral breastcancer [9].Since then many case reports have been published.

Murayama et al. [10] reported 37 cases of breast cancerassociated with NF1; most of the cases were diagnosedat an advanced stage and had invasive ductal carcinoma.The authors explained the advanced stage at the diagno-sis by the presence of cutaneous fibromatas in the trunkin most of the patients which could have delayed theearly diagnosis. In our cases, breast cancer was diag-nosed at an advanced stage in all of our patients (stageIIIA in two cases and IIIC in one case).In an earlier report by Nakamura et al. [5], the authors

noted that breast cancer affected young women (

Authors contributionsMA and MB treated one of the reported cases and contributed to theliterature review. HE and NB corrected the manuscript before submission. TKparticipated in its design and coordination and helped to draft the manuscript.All authors read and approved the final manuscript.

Received: 12 October 2014 Accepted: 28 January 2015

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AbstractIntroductionCase presentationConclusions

IntroductionCase presentationCase oneCase twoCase three

DiscussionConclusionsConsentAbbreviationsCompeting interestsAuthors contributionsReferences