www.elsevier.com/locate/breast

THE

BREAST

CASE REPORT

Breast metastases from colorectal carcinoma

Radu Mihaia,*, Jonathan Christie-Brownb, James Bristola

aDepartment of Surgery, Cheltenham General Hospital, Cheltenham, UKbDepartment of Pathology, Cheltenham General Hospital, Cheltenham, UK

Summary A case history is presented of a 53-year-old woman with an incidentalfinding of a breast lump, identified after having had chemotherapy for lungmetastases from a rectal carcinoma. Clinical examination, ultrasound, mammogra-phy, fine needle aspiration and core biopsies could not prove definitively whether thebreast lump represented a metastasis from colorectal carcinoma. Following localexcision, the final diagnosis of metastatic colorectal carcinoma to the breast wasbased on the absence of any site of origin within the breast (i.e. no surrounding DCIS)and on the expression of cytokeratin CK7 and CK20 on immunohistochemistry.Postoperative chemotherapy was initiated. Four months later, although without localrecurrence in the breast, the patient developed cutaneous metastatic deposits andactive treatment was stopped.A review of other cases of breast metastases from extramammary sources is

presented. Possible mechanisms for this rare and unusual phenomenon are discussed.& 2003 Elsevier Ltd. All rights reserved.

KEYWORDS

Breast;

Metastases;

Colorectal cancer

Case history

A 53-year-old woman presented to the Breast Clinicwith a 10-day history of a breast lump discoveredincidentally by the patient. She had no increasedrisk factors for breast cancer, hormonal or familial.A screening mammogram, 3 months prior toreferral was normal. Five years earlier she hadundergone an anterior resection for a Dukes’ Brectal carcinoma in another hospital, followed byhysterectomy and bilateral oophorectomy 2 yearslater for local recurrence of rectal carcinoma. Sixmonths prior to the discovery of the breast lump,she received chemotherapy for lung metastases.

Examination revealed a palpable nodule in thelower inner left breast, firm, not fixed, measuring

1 cm in diameter, with no associated lymphadeno-pathy. Ultrasound examination demonstrated reg-ular margins, without malignant features.Mammograms showed a well-defined mass lesion,not obviously malignant (Fig. 1). Fine needleaspiration cytology was suspicious of malignancy(C4). Core biopsies showed poorly differentiatedinfiltrating adenocarcinoma, with no signs ofintestinal differentiation. Although the suspicionof a metastasis from her previous colorectalcarcinoma was raised, it was not possible to ruleout a primary breast carcinoma on morphologicalcriteria on hematoxylin–eosin staining. Immunohis-tochemistry studies on the core biopsy specimensproved to be negative for oestrogen receptor,progesterone receptor, BCL-2 and HER-2. Bloodsamples for tumour markers were positive (CEA38 mg/l, CA125 70U/ml).

Excision biopsy of the breast lump was per-formed. On standard histological examination thetumour showed features of poorly differentiated

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*Corresponding author. University Department of Surgery,Bristol Royal Infirmary, Bristol BS2 8HW, UK. Tel.: þ 44-117-9701212x1259; fax: þ 44-117-9253726.E-mail address: r mihai99@hotmail.com (R. Mihai).

0960-9776/$ - see front matter & 2003 Elsevier Ltd. All rights reserved.doi:10.1016/S0960-9776(03)00125-5

The Breast (2004) 13, 155–158

adenocarcinoma with focal necrosis. There was noductal carcinoma in situ in the surrounding breasttissue. There was no evidence of intestinal differ-entiation. Immunohistochemistry for CEA was posi-tive, as expected in colorectal tumours but also insome breast carcinomas.

The patient restarted chemotherapy and 4months after surgery there were no signs of localrecurrence of the breast lesion. Subsequently shedeveloped cutaneous lesions over the left iliaccrest and within right groin, which on core biopsyshowed identical morphological features with thebreast tumour previously excised. Palliative carewas instituted.

The initial breast tumour was sent for analysis ofcytokeratin expression in another centre and theresults confirmed a pattern characteristic forcolonic tumours: CK20 positive–CK7 negative.

Review of the literature

Primary breast cancer is the leading cause of deathfrom malignant disease in women. Every year over32,000 new cases are diagnosed in the UK.Metastases to the breast from extramammarycarcinomas are extremely rare. In about 40% ofsuch patients, the breast lesion is the firstmanifestation of disease. The correct diagnosis istherefore crucial in these patients so that unne-cessary surgical interventions can be avoided.

Our patient presented to Breast Clinic whenknown to have loco-regional and widespreadmetastatic colorectal cancer. In this clinical con-text, the suspicion that her breast lump repre-sented a further metastatic deposit was very high.Unfortunately, slides of the primary rectal tumourwere not available for histological comparison.Furthermore, the findings on ultrasound and mam-mography (well-defined mass with regular margins)were in contrast with those reported by others. In aprevious study of patients with metastatic tumoursto the breast, mammography revealed poorlydefined lesions with obscured margins, whichon ultrasound examination appeared superficiallylocated, poorly defined, irregular and heteroge-neous.1

In the presence of widespread disease, theprognosis for this patient was poor when shepresented to our unit. It can be argued that oncethe diagnosis of a poorly differentiated infiltratingadenocarcinoma was proven on core biopsy, surgi-cal intervention could have been avoided. How-ever, in the absence of definitive proof that thebreast lesion represented disseminated diseasefrom the colorectal carcinoma, it was consideredthat the possibility of a primary breast carcinomacould not be excluded. Because at that stage theclinical condition of the patient was not severelyaffected, active management was pursued. Thiswas stopped when she developed further cutaneousmetastatic lesions.

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Figure 1 Imaging studies in a patient with a solitarybreast metastasis from a colorectal carcinoma: (a)ultrasound findings; (b) lateral view/ mammogram; (c)cranio-caudal view/mammogram.

156 R. Mihai et al.

For our patient the diagnosis was finally reachedafter studying the pattern of cytokeratin (CK)expression. Recently, expression of CK with differ-ent molecular weight has been found to helpidentify the origin of adenocarcinomas whosemorphological features do not allow to specify theinitial origin. Expression of CK7 and CK20 isconsidered to be most helpful in this algorithm.Some tumours express none of these cytokeratins(renal), some tumours express both cytokeratins(mucinous ovarian carcinoma, pancreatic carcino-ma, transitional cell carcinoma of the bladder).Importantly, the great majority of breast tumoursare CK7-positive and CK20-negative while color-ectal carcinomas are usually CK7-negative andCK20-positive.2

A review published in 1981 quoted that onlyabout 200 cases of metastases to the breast weredescribed in the literature at the time.3 Aliterature search identified a further 145 casesreported in 46 studies performed between 1980 and2000 (Table 1). It appears therefore that the totalnumber of patients reported in the English litera-ture to have metastases to the breast is under 400.The real incidence is difficult to know and isprobably much higher. This is suggested by datafrom an autopsy study that reported incidental

findings of breast metastases in patients withknown melanomas, ovarian, renal cell and gastricadenocarcinomas.4 Patients with breast second-aries from a colorectal primary neoplasm areextremely rare. Only six such patients havebeen reported in the last 20 years, two of thembeing in men.5–8

This rare incidence of metastases to the breastfrom tumours without any anatomical connectionto the breast raises questions about the possibleunderlying mechanisms for such events. Accordingto the widely accepted model, micrometastaticfoci arise from dissemination of clonogenic cellspossessing essentially similar characteristics to theprimary tumour. The spread of such cells ismediated by systemic circulation, lymphatic circu-lation or transcoelomic migration. This model doesnot explain the occurrence of solitary metastases inunusual sites such as the breast.

An alternative hypothesis of metastasis has beenproposed recently.9 Following death by apoptosis ofexisting cancer cells, discrete fragments of cellulargenome may be released into the circulation andsubsequently taken up by cells of the reticulo-endothelial system. Such fragments of geneticmaterial may be passed to other cells of thereticulo-endothelial system and possibly to othernormal cells via transfection. This could lead toexpression of oncogenic sequences and develop-ment of cancer cell phenotypes in unexpectedlocations. Such a mechanism could explain involve-ment of breast tissue in metastatic processes notexplained otherwise by the ‘‘classical mechan-isms’’. Further studies might shed more light onthis unorthodox hypothesis.

References

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3. Nielsen M, Andersen JA, Henriksen FW, et al. Metastases tothe breast from extramammary carcinomas. Acta PatholMicrobiol Scand (A) 1981;89(4):251–6.

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Table 1 Source of primary tumour in patients withbreast metastases.10–25

Lymphoma 23Melanoma 21Rhabdomyosarcoma 15Lung tumours 11Ovarian tumours 11Renal cell carcinoma 8Cervix carcinoma 7Leukaemia 5Thyroid 5Prostatic carcinoma 5Leiomyosarcoma 5Intestinal carcinoid 4Pancreaticadenocarcinoma

3

Mesothelioma 2Gastric carcinoma 2Plasma cell myeloma 2Individual cases: retroperitoneal

sarcoma,cholangiocarcinoma,squamos cell carcinomaof the skinperipheralneuroblastomaMeckel cell carcinoma

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19. Kiely N, Williams N, Wilson G, Williams RJ. Medullarycarcinoma of the thyroid metastatic to the breast. PostgradMed J 1995;71:744–5.

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