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Original study

Breast cancer with intraabdominal metastases. Is surgery


necessary?

Andrian Panuța1,2, Iulian Radu*,1,2, Ionuț Huțanu1,2, Ana-Maria Mușina1,2, Mihaela


Buna-Arvinte1,2, Mihaela Mădălina Gavrilescu1,2, Dragoș Viorel Scripcariu1,2, Viorel
Scripcariu1,2

1 2
Ist Surgical Oncology Unit, Iasi Regional Cancer Institute, Romania; Department of Surgery,
”Grigore T. Popa” University of Medicine and Pharmacy Iasi, Romania

Abstract
Metastatic breast cancer (MBC) has a very poor prognosis, considering the lack of reliable curative
medical or surgical approaches. Patients with stage IV breast cancer usually undergo palliative surgical
procedures and symptomatic treatment. In a 5-year period, 1258 patients with breast cancer were treated in
our surgical oncology unit. For the current study, we have selected 19 (1.43%) female patients with
intraabdominal metastases (peritoneal, hepatic, ovarian etc.) derived from breast cancer, which received at
least one surgical procedure in our unit. We compared our data with up-to-date reports and guidelines in order
to establish the role and further directions of surgery, and (most importantly) the necessity of surgery itself in
the management of this therapeutically disadvantaged patient-group. Even if current guidelines do not
recommend surgical treatment of intraabdominal metastases derived from breast cancer, several oncology
centers (including our unit) did not discard surgery, especially in patients with solitary metastasis.

Keywords: metastatic breast cancer, peritoneal metastases, liver metastases, ovarian metastases, unusual
origin metastases, cytoreductive surgery, HIPEC

Introduction advancements of chemo-, hormonal-, radio-


and targeted therapies [1].
Breast cancer (BC) is the most frequent On the other hand, metastatic breast
malignant tumor and the major cause of cancer does not benefit from any curative
cancer-related death among women. If procedures and therefore represents quite a
diagnosed in postmenopausal women, early challenge for breast surgeons and oncologists.
stages (Tis-2N0-1M0) and with a favorable Its incidence remained stable through the
biology (luminal molecular subtypes) BC years even if screening programs showed their
represents a perfect example of a curable efficiency, and breast cancer is diagnosed, in
cancer. Life expectancy for patients with the majority of cases, in the early stages (at
locally advanced or recurrent non-metastatic least in Western Europe). Apparently,
BC has also increased due to the metastases do not always occur in locally
advanced breast cancer. Another explanation
may be the fact that MBC affects younger
patients that are not included in breast cancer
Received: May 2018; Accepted after review:
screening programs [2].
November 2018; Published: December 2018.
*Corresponding author: Iulian Radu, Department The role of surgery in stage IV breast
of Surgery, Regional Oncology Institute, 35 Gral cancer with intraabdominal metastases is
Berthelot str., Iasi, Romania.
Email: raduiuli@gmail.com highly debatable. Widely recognized, up to
date guidelines for clinical practice (such as

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those published by the National uterine metastases (with or without extra-


Comprehensive Cancer Network (NCCN) [3] abdominal metastases). We have included
and the European Society for Medical MBC patients with one or more metastases
Oncology (ESMO)) [4] do not recommend located within the abdominal cavity, who were
primary breast tumor surgery or excision of hospitalized in our unit and underwent at least
metastases in MBC. In addition, there are no one surgical procedure.
randomized studies to assess the benefit of
axillary lymph node dissection and usually a Clinicopathological characteristics of the
sentinel node biopsy is performed for staging patients: The studied group contained 19
purposes. Nevertheless, several studies affirm female patients with an average age of 63
the possible benefit of breast surgery ranging from 46 to 76 years old. Urban/rural
(lumpectomy or mastectomy), this can be living environment was attested in equal
explained by the reduction of the tumor proportions. All patients received physical
burden, decreasing the level of circulating examination, mammary ultrasound and
tumor cells. This fact has a potential influence mammography, abdominal and pelvic
on the prognosis of metastatic breast cancer. ultrasound (with additional CT or MRI scans
However, in the majority of cases breast where needed) and were histologically
surgery, in such situations, is performed only if diagnosed preoperatively (core-biopsy) or
the tumor is symptomatic (ulcerated, infected, intraoperatively (extemporaneous exam). Most
hemorrhagic breast lump) [3-5]. patients were diagnosed with locally advanced
Besides breast surgery, as a general breast cancer (T3-T4). Twelve cases (1 case
surgery team, we perform a wide range of associated with adrenal metastasis) were
operations, mostly in the abdominal cavity, for diagnosed with liver metastases (Figure 1)
primary and secondary digestive, urologic and with or without extra-abdominal masses
genital cancers, which brings intraabdominal (lungs, bones, brain) and 7 cases with
metastases from breast cancer in our sphere peritoneal carcinomatosis (Figures 2 and 3a)
of interest. Our objective was to share the with or without ovarian secondary
experience of our unit in surgical treatment of dissemination (Figure 3b), and 1 case of
metastatic breast cancer in order to compare ovarian metastasis (without carcinomatosis).
our results with those shown by reference Eleven cases were considered as PMBC
surgical oncology centers. (primary metastatic breast cancer). In 8 cases,
metastatic disease occurred at an important
time-span from breast surgery (6 months - 4
Patients and Methods years). The predominant histological type (15
cases) was NST (no special type/invasive
In this study, we retrospectively analyzed ductal carcinoma), while 4 cases were of
cases of BC, who received surgical treatment invasive lobular carcinoma. Molecular
in our unit (First Surgical Oncology Unit, subtypes found in the study group: luminal B –
Regional Institute of Cancer Iasi, Romania). 10 cases, luminal A – 6 cases, triple negative
Over the course of 5 years (May 2012 - May – 2 cases and HER2-type – 1 case.
2017), a number of 1258 female patients were
operated in our unit for breast cancer. Treatment. All cases received pre- or
Nineteen cases (1.43%) of MBC were included postoperative chemotherapy ± antiestrogen
in or study. These patients showed peritoneal therapy and, in locally advanced stages,
carcinomatosis, liver, ovarian, adrenal, and palliative external radiotherapy.

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Fig. 1. Liver metastases from breast cancer

Fig. 2. Peritoneal carcinomatosis from breast cancer

Fig. 3. Peritoneal carcinomatosis (a) and ovarian metastasis (b) derived from breast cancer

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Surgical treatment applied on our BC metastatic disease. Another patient with a


patients with intraabdominal metastases solitary ovarian metastasis (without PC)
(Table 1) had mainly a palliative intent. Only underwent a hysterectomy with bilateral
one patient had a solitary hepatic metastasis anexectomy with curative intent. In 10 cases,
which was feasible for R0 resection. In seven palliative surgery of primary breast tumor was
cases, breast cancer surgery was performed 6 performed.
months to 4 years prior the occurrence of

Table 1. Surgical procedures performed in our unit for patients Stage IV breast cancer with intraabdominal
metastases

Surgery performed on the primary breast tumor No. %


Subcutaneous mastectomy 1 5.26
Total/„cleansing” mastectomy 4 21.05
Bilateral total mastectomy 1 5.26
Madden’s modified radical mastectomy 2 10.52
Lumpectomy 2 10.52
Excision of the recurrent prepectoral tumor 1 5.26
Core-biopsy (alone) 2 10.52
No breast surgery (primary tumor being operated before the admission to our unit) 6 31.56

Surgery performed on the metastases from breast tumor No. %


Hepatic metastasectomy (partial IV segmentectomy) 1 5.26
Subtotal hysterectomy with bilateral anexectomy 2 10.52
Unilateral anexectomy 1 5.26
Laparoscopic peritoneal biopsy 1 5.26
Terminal colostomy (for occlusive syndrome caused by PC) 1 5.26
von Hacker’s gastroenterostomy (for upper gastrointestinal obstruction syndrome 1 5.26
caused by PC) and multiple peritoneal biopsies
No surgery on metastases 11 57.89

Follow-up: Our patients were followed-up patient underwent a subtotal hysterectomy


every 3 months in first 2 years and every 6 with bilateral anexectomy. The pathological
months during the third-fifth years after result was surprising – Microscopy: ovarian
surgery, by physical examination (both by a and tubal fragments (containing many
surgeon and an oncologist), tumor marker mesonephric debris) with diffuse carcinoma
CA15.3 determination and bilateral breast and infiltration with trabecular and cordial
abdominal ultrasound. Also in some cases architecture and discoesic alveolus, reduced
mammography, thoracic-abdominal CT and associated stroma and major edema.
bone scintigraphy were performed. Immunohistochemistry (IHC): EMA, CK7, ER,
Outcomes: Only 7 out of 19 patients in the PR, MUC5AC, GCDFP15, Mammaglobin,
study group survived (overall survival – CK20 – positive in tumor cells. TTF1, CDX2 –
36.8%). negative in tumor cells. E-cadherin – positive
From our patients’ database, we would in tumor cells. HER2neu – negative. Ki67 –
mention some cases that do not fit the disease positive in about 20-22% of tumor cells.
evolution patterns. Diagnosis: The histological and IHC aspects
described advocate for a carcinomatous
Case 1. A 55-years-old female patient was infiltration within a carcinoma metastasis with
admitted to our unit for performing a a mammary gland origin. Further
cytoreductive surgery for a high suspicion of investigations revealed bilateral multicentric
stage IIIC ovarian carcinoma (left ovarian breast cancer. After the patient underwent 6
tumor, an important amount of ascites, cycles of chemotherapy (Cyclophosphamide
multiple nodules of peritoneal carcinomatosis 1000mg + Epirubicin 150mg) combined with
revealed on CT scan, increased level of hormonal treatment (Tamoxifen), a bilateral
CA125 tumor marker (677 units/mL)). The total mastectomy was performed (Pathology

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result: NST invasive carcinoma pT3mNxG1 Discussions


(left breast), pT2mNxG1 (right breast)). We
regularly followed this patient for more than 4 Nowadays, breast cancer surgery has
years. She presents no signs of local evolved, offering high rates of long-term
recurrence or systemic disease progression. survival and an acceptable quality of life
Case 2. A 52-years-old female patient known (breast conserving surgery, immediate breast
with radically operated, chemo-treated right reconstruction etc.) for BC patients.
breast cancer (in another institution) was Unfortunately, metastatic breast cancer (MBC)
admitted (18 months after the initial diagnosis remains a life-threatening condition with no
of BC) in our unit in order to evaluate a hepatic appropriate therapeutic solutions. During their
tumor mass revealed on a CT-scan (solitary lifetime, 20 to 40% of BC patients will develop
16/17/19 mm-sized hepatic tumor located in metastatic disease [2, 6]. Up to 10% of stage
the fifth hepatic segment), performed because IV breast cancers prove to be primary
of an increased level of CA15.3 tumor marker metastatic – metastases being diagnosed
(55.82 units/mL). The patient underwent simultaneously with primary breast tumor [2].
surgery; intraoperatively, the location of the The dissemination of metastases is frequently
liver mass proved to be in the fourth posterior multiorganic. Preferred dissemination sites
segment – a partial hepatic segmentectomy include bones (67%), lungs (31%), liver (35%),
was performed. The pathology examination brain (11%), skin (7.5%) and other sites
confirmed the breast cancer origin of the (peritoneum (7.6%), ovary (1.5%), etc.) [1, 2].
hepatic metastasis (microscopy: a hepatic Locoregional treatment of MBC. NCCN
fragment exhibiting adenocarcinoma and ESMO guidelines do not recommend any
metastasis with tubular architecture and kind of surgery of primary or secondary tumors
reduced stroma. IHC: CK7 – positive in less with curative intent, since there are no
than 20% of tumor cells. Mammaglobin, randomized studies to demonstrate its survival
GCDFP15 – positive in tumor cells. ER, PR – benefits in comparison to chemotherapy alone
diffusely and intensely positive in tumor cells. [3-6]. The only recommended surgery in MBC
Ki67 – positive in about 15% of tumor cells. is bilateral oophorectomy in luminal molecular
HER2neu – negative in tumor cells. CK20 - subtypes (ER/PR positive) in premenopausal
negative in tumor cells. Conclusion: The women and palliative (“cleansing”) total
described aspects advocate for the diagnosis mastectomy in case of locally advanced,
of metastasis with a mammary gland origin). ulcerated, infected or hemorrhagic breast
We regularly followed this patient for more cancer [4, 5]. We should mention that in the
than 2 years. She presents no signs of local majority of BC patients diagnosed with
recurrence or systemic disease progression. metastatic disease, primary breast tumor and
Case 3. A 47-years-old female patient known axillary surgery have already been performed,
with radically operated, bilateral metachronous detectable metastases usually occurring
breast cancer (with bilateral breast several months or years after diagnosis. In
reconstruction in another institution), under case of PMBC, the role of surgery of primary
continuous antiestrogen therapy, was admitted breast tumor is minor. In non-locally advanced
to our unit in order to evaluate the cause of a cases a core-biopsy is usually the only
recently appeared menometrorrhagia. surgical procedure needed, the patient only
Abdominal CT and MRI scans revealed receiving chemotherapy alone [7].
multiple bone metastases, an ovarian tumor The role of surgery in hepatic metastases
and a tumorous mass in the cervix. The derived from BC. Although the liver is the most
patient underwent unilateral oophorectomy common intraabdominal site of breast cancer
and cervical biopsy. Both of these organs metastases (hepatic metastases found in up to
proved to be metastatic sites for breast 75% of patients deceased due to BC) the
carcinoma. The patient’s evolution was frequency of solitary liver metastasis is low (3-
unfavorable. The particularity of this case is 9%). Traditionally chemotherapy and surgical
the very rare site of metastases from breast treatment of MBC cases have a palliative
cancer, namely the cervix. intent only. There are no randomized studies

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demonstrating the advantages of the excision intraperitoneal chemotherapy (HIPEC) with a


of intraabdominal metastases derived from BC curative intent with encouraging outcomes.
in comparison with chemotherapy alone. Current guidelines show no indications for this
However, MBC patients with single liver procedure in MBC patients with peritoneal
metastases can become candidates for secondary determinations, but there are
metastasectomy [8]. There are several ongoing studies that applied HIPEC in limited
publications attesting an increase in survival series of patients with promising initial results
among patients with isolated hepatic [14, 15].
metastases from BC who underwent hepatic
resections. The survival benefit of this
procedure mainly depends on the dimensions Conclusions
of the hepatic tumor (<5 cm in diameter), on
the molecular biology of BC (better outcomes Intraabdominal metastatic disease rarely
in hormone responsive molecular subtypes) occurs in the progression of breast cancer and
and on the menopausal status of the patients is usually associated with a locally advanced
(better results for patients older than 50 breast tumor (in our study, especially liver
years). The response to neoadjuvant chemo- metastases associated with more frequent
and/or hormonal therapy is also an important sites: lungs, bones, brain). Peritoneal
selection criterion for eventual hepatic carcinomatosis, ovarian metastases more
metastasectomy. Patients with primary often occur over a time span (on average 2
metastatic diseases have poorer prognosis years in our study) from breast surgery. The
and benefit less from hepatectomy than those lobular type of breast carcinoma tropism for
in whom liver metastasis occur more than one serous membranes is evoked in literature and
year after breast cancer diagnosis [5, 8, 9]. we obtained similar results (4 of 6 cases with
Despite related criteria of selection of the PC revealed a lobular invasive breast
candidates for hepatectomy in MBC, a few carcinoma origin). Routinely used – abdominal
single institution studies report favorable initial ultrasound can identify eventual liver
results in patients with more than one liver metastases, but has a poor specificity in
metastases, and more than that, even perform detecting early peritoneal metastases. An
re-resection of hepatic metastases derived abdominal CT scan for all patients diagnosed
from BC [10, 11]. with breast cancer would certainly increase the
The role of surgery in peritoneal management costs, but would also
carcinomatosis derived from BC. Peritoneal significantly contribute to the detection of
carcinomatosis (PC) is a diagnosis with a very primary metastatic breast cancer and to early
poor prognosis and usually these patients diagnosis of intra-abdominal metastases from
receive palliative chemotherapy and breast cancer. The majority of stage IV breast
symptomatic care [12]. PC usually occurs in cancer patients treated in our unit were cases
patients with cancers of the digestive tract or of primary metastatic breast cancer, which has
of the female genital system. Recent papers more unfavorable outcomes than cases with
evoked lobular invasive histologic type, high metachronous metastases. This fact explains
tumor grade, locally advanced cases as risk very poor survival rates in the studied group.
factors for breast cancer peritoneal The role of surgery in metastatic breast cancer
metastases [13]. Survival rates in this group of is controversial and currently, in the majority of
patients are comparable to BC patients with cases, it has either palliative intent or has no
brain metastases [10]. In specialized surgical benefits at all. The combination of targeted
oncology centers (including our unit) therapy and cytoreductive surgery as well as
accurately selected patients with primary the use of HIPEC in the treatment of
peritoneal malignant tumors (i.e. peritoneal metastatic breast cancer (with peritoneal
mesothelioma and peritoneal pseudomyxoma carcinomatosis) is the subject of ongoing
peritonei) and PC derived from colon or clinical trials.
ovarian cancers receive optimal cytoreductive
surgery accompanied by hyperthermic

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Consent Competing interests


Written informed consent was obtained from the The authors declare that they have no competing
patient for publication of this case report. interests.

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