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\begin{document}

\title{A rare case of lobular breast cancer metastasising to large bowel}



\author[1]{Waka Yanagisawa}%
\author[2]{Sandra Krishnan }%
\author[2]{Adrian Fernandez }%
\affil[1]{Affiliation not available}%
\affil[2]{Bega - South East Regional Hospital}%


\vspace{-1em}



  
  \date{June 16, 2024}


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\begin{abstract}
Lobular breast cancer is rarely known to metastasise to the
gastrointestinal tract. This article explores a case of a patient in
remission from lobular breast cancer, who presented with bowel
obstruction secondary to metastatic lobular cancer.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Breast cancer is the most common malignancy in women, most frequent in
the fourth and fifth decades of life and comprises 27\% of all
cancers\textsuperscript{2}. Since the introduction of the national
breast screening programme and earlier detection, only 7\% of breast
malignancies have metastasised at the time of
presentation\textsuperscript{2}. Breast cancer most commonly metastasise
to lungs, bones, liver and brain. On rare occasions, invasive lobular
carcinoma (ILC) has been demonstrated to metastasise to the
gastrointestinal tract. We describe a case of a patient in remission
from lobular breast cancer who presented with metastatic lobular breast
carcinoma requiring an extended right hemicolectomy. As there is still a
lot to be learnt in regard to metastatic spread of the disease,

this case report raises the discussion regarding benefits of
investigating patients with known invasive lobular breast cancer through
screening endoscopy, for potential gastrointestinal metastases.

\textbf{Case Report}

A 78-year-old female presented with a one-month history of colicky
abdominal pain, vomiting and unintentional weight loss. Her past medical
history included ischemic heart disease on clopidogrel and previous
history of deep vein thrombosis. She recently returned a positive stool
occult blood test, awaiting colonoscopy. Her past surgical history
included a hysterectomy, cholecystectomy, appendectomy and notably, a
right lobular breast cancer for which she had undergone a wide local
excision and sentinel lymph node biopsy in 2018. Her breast tumour was a
Stage IIB, 41mm grade 2 lobular type breast cancer (ER/PR positive, HER
2 negative, Ki-67 of 4\%) with one third of the biopsied lymph nodes
positive. She received adjuvant radiotherapy over 6 weeks and hormonal
therapy letrozole which was discontinued after 7 months due to
arthralgia severely impacting her quality of life. Tamoxifen was deemed
unsuitable due to associated risk of thromboembolism and her previous
history of deep vein thrombosis. She continued regular outpatient
surveillance and was in remission, confirmed by a normal breast
ultrasound and mammogram a year prior to presentation.

An Abdominal Computed Tomography on presentation demonstrated concentric
wall thickening and narrowing of the distal transverse colon with
dilatation of the proximal transverse colon and ascending colon,
concerning for a neoplastic lesion (Figures 1, 2). Subsequent
investigation with a colonoscopy revealed a circumferential lesion in
the proximal descending colon, not typical in appearance for an
adenocarcinoma. It was difficult to negotiate past the tumour and
biopsies were taken. This revealed features suggestive of a sessile
serrated adenoma. A semi-urgent laparotomy was performed in view of her
progressive abdominal symptoms and found the offending, thickened
segment to involve the distal transverse colon and splenic flexure. An
extended right hemicolectomy was performed, and her surgery was routine.
Histopathology revealed a circumferential, firm, ill-defined partially
ulcerated lesion measuring 25 x 20mm that was demonstrated to be a
metastatic, grade 2 lobular carcinoma deposit. The tumour was centred
primarily in the muscularis with extension to the mucosa and subserosa.
Lymphovascular was present and three separate extranodal deposits of
metastatic lobular carcinoma were seen in the mesenteric tissue. The
immunohistochemistry demonstrated ER and PR positive status, HER2 ISH
negative and a Ki-67 of 18\% in keeping with the previous lobular breast
carcinoma histopathology.

She recovered well post-operatively, requiring a short period of
rehabilitation. She was re-referred to the oncology service where she
was reviewed one month post-operatively. She was recommenced on
letrozole to reduce the risk of further recurrence and associated issues
including ascites and pleural effusion. She was not a candidate for
chemotherapy given her frailty. Unfortunately, prior to further
follow-up, she passed away, two months post-operatively with increasing
anorexia and fatigue.

\textbf{Discussion}

ILC accounts for 10\% of all breast cancers, and is the second most
common breast carcinoma \textsuperscript{1,3}. The incidence is
increasing in postmenopausal women, possibly secondary to the use of
hormone replacement therapy in this age group \textsuperscript{3}.
Breast cancer frequently metastasises to skeletal and pulmonary systems
however rarely to the gastrointestinal tract. However lobular breast
cancer more frequently metastasise to the gastrointestinal
tract\textsuperscript{4}. In a study of 2605 cases of breast cancer with
metastases; 359 lobular and 2246 with ductal carcinoma, 4.5\% in ILC
metastasised to the gastrointestinal tract compared with 0.2\% in the
ductal carcinoma group \textsuperscript{5}. Gastrointestinal tract
involvement with metastatic ILC are thought to most commonly involve
stomach and small bowel, then followed by colon and
rectum\textsuperscript{3}. According to available literature, 60\%
metastasises to the stomach, 12\% to the oesophagus, 11\% to the colon,
8\% to the small intestine and 7\% to the rectum \textsuperscript{6}.
Due to high expression of steroid hormone receptors in lobular breast
cancer, adjuvant endocrine treatment is the preferred treatment for
ILC\textsuperscript{7}. Patients are characterised by poor prognostic
profile and few survive longer than two years following
metastasis\textsuperscript{1,8}. The reasons for this mechanism of
spread are unclear however may possibly include the histopathology of
ILC. ILC is characterised by small cells that infiltrate the breast
stroma in a single-file `Indian-file' pattern which does not destroy
anatomical structure nor result in a reactive connective tissue response
(Figure 3), and can therefore fail to distinctly form a mass in the
breast which can be difficult to identify early \textsuperscript{3}.
This may account for the higher distant metastatic rate in ILCs
\textsuperscript{9}. Other reasons for metastasis of lobular breast
cancer may be explained by E-cadherin which is crucial in the
maintenance of epithelial cell polarisation. E-cadherin is a calcium
dependent epithelial cell adhesion molecule when mutated or lost can be
associated with metastases as it acts as an invasion suppressor
\textsuperscript{10}. Deficiency of this molecule is responsible for
cancer metastasis due to loss of cell to cell adhesion, with increased
cell motility causing spread in blood and lymphatics
\textsuperscript{7}. In lobular breast cancer, E-cadherin loss has been
observed in most cases but not observed in invasive ductal cancers. In
some studies, E-cadherin has been used to be reliably used as a marker
to differentiate between IDC and ILC \textsuperscript{(11)}. This may
account for its aggressive behaviour compared with
IDC.\textsuperscript{10}. However poor prognostic factors include age
over 70 years, and degree of nodal involvement, which are associated
with significant increased risk of relapse and death
\textsuperscript{12}, which in this case may have increased her risk of
poorer outcome. The rarity of the disease and the uncertainty of the
nature of ILC makes this an intriguing field, requiring further research
and thoughtful consideration in order to most appropriately manage
patients. Patients diagnosed with breast ILC and particularly those
above 70 years of age, should be carefully monitored for any evidence of
potential gastrointestinal metastases through imaging or screening
colonoscopy.

\textbf{Conclusion}

Patients with gastrointestinal symptoms with known invasive lobular
breast cancer should be adequately investigated for potential metastases
through imaging or gastroscopy and colonoscopy, to rule out presence of
gastrointestinal metastases. Particular attention to the subtype of ILC
and prognostic factors including age and nodal involvement, should alert
clinicians to the likely possibility for gastrointestinal metastases.
Knowledge of this unusual pattern of disease will help plan appropriate
treatment, in order to optimise prognosis.

\textbf{Acknowledgements}

The authors thank Dr Jonathan A Smiles, Pathologist for his contribution
to the paper.

\textbf{Conflict of interest}

None declared

\textbf{Ethical approval}

This study does not require any ethical committee approval.

\textbf{Author contribution}

WY, SK and AF were all involved in reviewing the literature, prepared
and edited the manuscript and all authors approved the final version of
the manuscript.

\textbf{References}

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metastasis to the colon, appendix and the gallbladder Breast
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2. Miller T. 2013 Unexpected Diagnosis of Both Adenocarcinoma of the
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10. Younis L, K., Sakka, H, E., Haque, I. The Prognostic Value of
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11. Kanthilatha, P., Baliga, P., Shrestha, B. 2013. E-Cadherin
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12. Lorfida M, Maiorano, E., Orvieto, E., Maisonneuve, P., Bottiglieri,
L., Rotmensz, N., Montagna, E., Dellapasqua, S., Veronesi, P.,
Galimberti, V., Luini, A., Goldhirsch, A., Colleoni, M., Viale, G.
Invasive Lobular Breast Cancer: Subtypes and Outcome. 2012. Breast
Cancer Research and Treatment;133:713-23.\selectlanguage{english}
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