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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: J Surg Res. 2020 Jul 22;256:212–219. doi: 10.1016/j.jss.2020.06.022

Treatment and Outcomes of Early Stage Breast Cancer in Patients with Hepatic Dysfunction

Yulia B Olimpiadi 1, Kirstyn E Brownson 1, Jeffrey A Kahn 2, Brian Kim 2, Hyosun Han 2, Saro Khemichian 2, Tse-Ling Fong 2, Irene Kang 3, Alicia Terando 1, Julie E Lang 1
PMCID: PMC7854813  NIHMSID: NIHMS1607288  PMID: 32711178

Abstract

Background

There exists a dogma of surgical nihilism for patients with cirrhosis and breast cancer causing de-escalation of surgery and impacting survival. We hypothesized that breast cancer surgery would not result in a significant change in the Model for End-Stage Liver Disease-Sodium (MELD-Na) scores pre- and post-surgery.

Methods

We performed a single institutional retrospective review of medical records from January 2013 to July 2019 of patients with concurrent cirrhosis and breast cancer. We used the non-parametric Friedman test to compare differences in MELD-Na scores.

Results

Eight patients with both cirrhosis and breast cancer were identified. Median follow up was 30.5 months. Half of the patients had Child-Pugh Class A cirrhosis and half had Child-Pugh Class B cirrhosis. Six (75%) patients underwent lumpectomy and two (25%) underwent mastectomy. There was no statistically significant difference (p=0.66) in median MELD-Na score pre- (16) and post-surgery (18). Two (25%) patients experienced post-operative complications. Three patients were listed for liver transplantation. Out of three listed patients, two (25%) patients underwent successful liver transplantation after breast surgery. One (12.5%) patient died without transplant. Three (37.5%) patients were alive greater than 5 years after breast cancer diagnosis without evidence of cancer recurrence. The eighth patient has remained breast cancer free for over 6 months since her surgery.

Conclusions

Surgery for patients with Child-Pugh Class A and B cirrhosis and early stage breast cancer did not result in a significant change in MELD-Na score pre- and post-surgery, suggesting that selected patients may benefit from breast cancer surgery with curative intent.

Keywords: breast cancer, breast cancer surgery, cirrhosis, hepatic dysfunction, liver transplant, liver failure

Introduction

Breast cancer is not uncommon in cirrhotic patients. Breast cancer rates in patients with cirrhosis are at least comparable to, and potentially even higher than, the general population given elevated estrogen levels in patients with liver cirrhosis. (1, 2) There exists a paucity of published evidence to guide recommendations for or against breast surgery in cirrhotic patients. Deescalation of breast cancer surgery due to surgical nihilism could adversely impact survival, as liver transplantation for worsening hepatic function would not routinely be offered to patients with active malignancy. (3, 4) Recognizing that some early stage breast cancers may have a favorable prognosis, we aimed to address the risks and benefits of surgery in the setting of Child-Pugh Class A or B cirrhotic patients with Stage 0 and Stage I breast cancer, taking into account that cirrhosis has a greater risk of mortality compared to most major cancers. (5) According to the National Comprehensive Cancer Network Guidelines, breast cancer treatment, including surgery, should be individualized based on the comorbid conditions in order to maximize the benefit and minimize the risk for these patients. (6)

The pre-transplant assessment in cirrhotic patients without liver cancer is designed to avoid organ transplantation in patients with an extrahepatic cancer diagnosis, as transplantation and subsequent immunosuppression will not improve, and could potentially hinder, the patient’s prognosis from the cancer. Transplant evaluation decreases rates of placing scarce organs into recipients with a limited prognosis. (2) Solid organ allocation policies emphasize the utility of a transplant. Post-transplant malignancy (PTM) is one of the leading causes of late death in transplant patients. (8) Therefore, it is expected that the United Network for Organ Sharing (UNOS) would exclude patients with pre-existing neoplasms, including breast cancer, from transplantation.

While there are breast cancer patients with a diagnosis of cirrhosis who go on to become liver transplant recipients, we found no published studies in the medical literature that evaluated the short-term complication rates or outcomes associated with early stage breast cancer surgery in the setting of cirrhosis. We hypothesized that breast cancer surgery would not cause statistically significant differences in the Model for End-Stage Liver Disease-Sodium (MELD-Na) scores pre- and post-surgery. MELD-Na scores, complication rates, post-surgical length of hospital stays, and readmission rates in cirrhotic patients who underwent breast cancer surgery were evaluated. Rates of subsequent liver transplant listing and receipt of transplantation, incidence of death without transplantation, and short-term rates of breast cancer recurrence were also assessed.

Material and methods

We retrospectively queried the electronic medical records at a single academic institution, Keck Hospital of the University of Southern California (USC), between January 2013 and July 2019. Our institution is a high-volume center for solid organ transplantation, including liver transplantation. It includes the USC Norris Comprehensive Cancer Center that provides care for many breast cancer patients with serious co-morbidities, including cirrhosis. After approval by the USC Institutional Review Board (HS-17–00525), including an authorization of a waiver of informed consent, we reviewed charts of patients satisfying study criteria. We collected data on patient age at time of breast cancer diagnosis, etiology of the patient’s hepatic dysfunction, clinical cancer stage, tumor grade, hormone receptor status, human epidermal growth factor receptor 2 (Her2) status, time from diagnosis to surgery, type of surgery performed for breast cancer, MELD-Na score at time of diagnosis and post-operatively, Child-Pugh Score at time of diagnosis and post-operatively, post-operative complications, hospital length of stay, readmissions, deaths, need for additional surgery in order to obtain clear margins, pathologic cancer stage, OncotypeDx Recurrence Score (Genomic Health, Redwood City, CA), adjuvant cancer treatments including endocrine therapy, radiation therapy, and chemotherapy, documentation of transplant listing, receipt of liver transplant, type of transplant received (deceased versus living donor), date of transplantation, date of last follow-up, and evidence of breast cancer recurrence (Table 1). We used the non-parametric Friedman test to compare differences in the MELD-Na scores at the time of the breast cancer diagnosis and in the perioperative timeframe within the first 30 days after breast cancer surgery using GraphPad Prism (GraphPad Software Inc, San Diego, CA).

Table 1.

Clinicopathologic Characteristics

Patient ID Age at surgery Follow up (years) Cancer type c stage p Stage ER PR HER2 Day(s) at hospital MELD-Na at diagnosis Child score at diagnosis MELD-Na After surgery Child score before surgery Transplant Status
Patient 1 67 6.3 IDCA, DCIS cT1N0M0 (IA) ypT0N0M0 (0) 80 100 0 1 16 A 24 A transplanted
Patient 2 65 1.9 IDCA, DCIS CT2N0M0 (HA) pT2N0M0 (HA) 100 80 0 2 23 B 18 B listed
Patient 3 68 3.2 IDCA, DCIS cT1N0M0 (IA) pT1bN0M0 (IA) 100 100 0 0 19 B 23 C transplanted
Patient 4 60 1.7 DCIS cTisN0M0 (0) pTisN0M0 (0) 100 98 n/a 1 7 A 6 A not listed
Patient 5 58 5.7 ILCA cT1N0M0 (IA) pT1cN0(i+)M0 (IA) 99 50 0 0 16 B unknown unknown not listed
Patient 6 57 0.7 IDCA, DCIS cT1N0M0 (IA.) pT1cN0M0 (IA) 100 98 0 3 21 B 23 C Passed away before getting listed
Patient 7 47 6.1 ILCA cT1N0M0 (IA) pT1cN0M0 (IA) 100 100 0 0 11 A 9 A not listed
Patient 8 64 0.1 DCIS cTisN0M0 (0) pTisN0M0 (0) 95 90 n/a 2 14 A 15 A not listed
Patient ID Definitive surgery Surgery length Length of stay (days) Perioperative complications Oncotype Dx score Adjuvant endocrine therapy Adjuvant XRT Patient status: alive Type of transplant Local or distant recurrence
Patient 1 R total mastectomy, R SLNB 1:34 1 none not sent AI N Y living donor liver none
Patient 2 R wire localized segmental mastectomy, R SLNB 1:16 2 none 27 AI Y Y none none
Patient 3 R wire localized segmental mastectomy, R SLNB 1:58 0 none 4 AI Y Y DD liver/kidney none
Patient 4 L wire localized segmental mastectomy 1:36 1 none not sent AI N Y none none
Patient 5 R wire localized segmental mastectomy, R SLNB 3:16 0 none 18 AI Y Y none none
Patient 6 L total mastectomy, L SLNB 1:12 3 encephalopathy 33 AI N N none none
Patient 7 L wire localized segmental mastectomy, L SLNB 2:33 0 none not sent T Y Y none none
Patient 8 R wire localized segmental mastectomy 1:22 2 Tachycardia, low platelet count (46), one platelet transfusion not sent AI Y Y none none
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Abbreviation key: c stage = clinical stage, p stage = pathologic stage, ER = estrogen receptor, PR = progesterone receptor, HER 2 = Herceptin receptor 2, MELD-Na = Model forEnd-Stage Liver Disease Sodium, XRT = radiation therapy; AI = aromatase inhibitor, Y=yes, N=no; DD = deceased-donor; IDCA = invasive ductal carcinoma; DCIS = ductalcarcinoma in situ; ILCA = invasive lobular carcinoma; R = right; L = left; SLNB = sentinel lymph node biopsy

Results

We identified all patients between 18 and 80 years of age who had concurrent diagnoses of cirrhosis and breast cancer between January 2013 and July 2019 (n = 66). To our knowledge, among these 66 patients, 58 did not undergo surgery. Eight patients with a diagnosis of cirrhosis and breast cancer had breast cancer surgery. All patients were female with a median age of sixty-two at the time of breast cancer surgery. At the time of the breast cancer diagnosis, four (50%) were classified as having Child-Pugh Class A, and four (50%) as having Child-Pugh Class B cirrhosis. The median time from breast cancer diagnosis to definitive surgery was 55 days. The median patient follow-up was 30.5 months. The clinicopathologic characteristics of the patients are summarized inTable 1. Additionally, the characteristics of the two subgroups according to Child-Pugh class are compared in Table 2. Review of the final surgical pathology revealed that three (37.5%) patients were pathologic Stage 0, four (50%) patients were pathologic Stage IA, and one (12.5%) patient was Stage IIA. Of note, one of these patients with invasive breast cancer who had clinical IA stage on core needle biopsy underwent neoadjuvant treatment with endocrine therapy and her surgical pathology did not demonstrate residual cancer. Of patients with invasive breast cancer on final surgical pathology, three (37.5%) had invasive ductal carcinoma and two (25%) patients had invasive lobular carcinoma. OncotypeDx Recurrence Score testing was performed for four (80%) of the five patients with invasive cancer on final surgical pathology. The median OncotypeDx Recurrence Score was 22.5 (4–33) indicating a generally low risk of recurrence at 10 years with endocrine therapy alone. Of the four patients for whom an OncotypeDx Recurrence Score was obtained, two (50%) patients had high-risk recurrence scores (> 25) (Table 1). All patients had negative margins on final pathology, and none required additional breast surgery. No patients underwent breast reconstruction or oncoplastic surgery given the documented plan for a short duration of anesthetic for surgery. The operative time ranged from 1.2 – 3.2 hours with a median time of 1.4 hours, and a mean time of 1.8 hours. All patients except one underwent general anesthesia. The patient who underwent laryngeal mask airway had a breast conserving surgery for invasive ductal carcinoma in the setting of Child B cirrhosis with a MELD score equal to 19.

Table 2.

Clinicopathologic Characteristics of Child A/B subgroups

Variable Child A (n=4) Child B (n=4)
Median age 62.0 61.5
Median follow up (months) 46.0 30.4
Breast cancer type DCIS, DCIS, IDCA, ILCA Mixed (IDCA, DCIS), Mixed (IDCA, DCIS), Mixed (IDCA, DCIS), ILCA
Pathologic stage ypT0N0M0 (0) pT2N0M0 (IB)
pTisN0M0 (0) pT1bN0M0 (IA)
pT1cN0M0 (IA) pT1cN0(i+)M0 (IA)
pTisN0M0 (0) pTlcN0M0 (IA)
Breast surgery R total mastectomy and R SLNB R WL segmental mastectomy and R SLNB
L WL segmental mastectomy R WL segmental mastectomy and R SLNB
L WL segmental mastectomy and L SLNB R WL segmental mastectomy and R SLNB
R WL segmental mastectomy L total mastectomy and L SLNB
Median surgery time (minutes) 92 97
Median hospital length of stay (days) 1 1
Transplant surgery and listing status Living donor liver DD liver/kidney
Not listed, not listed, not listed Listed, not listed, not listed
Readmission within 30 days none none
Complications Tachycardia Encephalopathy
Thrombocytopenia
Pre-operative median MELD 12.5 21
Post-operative median MELD 12.0 23
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Abbreviations: DCIS = ductal carcinoma in situ; IDCA = invasive ductal carcinoma; ILCA = nvasive lobular carcinoma; R = right; L = left; WL = wire localized; p = pathologic, y = post-neoadjuvant, DD = deceased donor; SLNB = sentinel lymph node biopsy; MELD-Na = Model for End-Stage Liver Disease – sodium

No patients received neoadjuvant or adjuvant chemotherapy, even in the setting of high OncotypeDx Recurrence Scores. Cirrhosis precluded consideration of chemotherapy due to the risk of hepatic decompensation and was considered an absolute contraindication to chemotherapy. Out of eight patients, six underwent breast conserving surgery. Five patients had invasive carcinoma, and therefore were recommended radiation treatment. The sixth patient had DCIS, and although the patient met with a radiation oncologist, a decision was made to forego post-operative radiation due to a low local recurrence rate (less than 5%). Therefore, a total of five out of six (87.5%) patients received adjuvant radiation therapy at our institution. All patients in this study had estrogen receptor positive tumors, and 100% of the patients received endocrine therapy. Seven out of eight of the patients who received endocrine therapy were treated with an aromatase inhibitor.

The primary outcome assessed in this study was a change in MELD-Na score of the cirrhotic patients following breast cancer surgery. As hypothesized, the MELD-Na did not increase significantly post-operatively compared to the pre-operative MELD-Na score at time of breast cancer diagnosis (p=0.66). Specifically, the median MELD at time of breast cancer diagnosis was 16 (7–23), and the median MELD-Na in the post-operative period was 18 (6–24). (Figure 1) Secondary outcomes assessed were the rates of complication and readmission, length of hospitalization, patient death, breast cancer recurrence, rate of transplant listing, and rate of liver transplantation. Two (25%) patients had post-operative complications. One patient was found to have worsened thrombocytopenia and tachycardia on post-operative day 1, and one patient developed mild encephalopathy on post-operative day 1. The first patient was assessed and was found to be normotensive with adequate urine output and no signs of bleeding. Her electrocardiogram revealed sinus rhythm without evidence of cardiac ischemia. She received a transfusion of one pack of pooled platelets, which normalized her platelet count and her heart rate. She was discharged on post-operative day 2. The second patient was found to be confused, was administered her home medication of lactulose, and her symptoms resolved. She was discharged on post-operative day 2. There were no hospital readmissions within 30 days of surgical intervention for any of the eight patients. The mean hospital length of stay was 1.1 days. There was one patient death (12.5%) which was attributed to worsened hepatic decompensation without transplantation. There was no evidence of breast cancer recurrence in any of the patients in this cohort at last documented follow-up. Finally, at the time of this study, two (25%) patients underwent successful liver transplantation 7.5 and 18.9 months after breast cancer surgery and one (12.5%) additional patient was listed for liver transplantation 22 days later. Both patients who underwent liver transplantation had developed hepatic dysfunction secondary to nonalcoholic steatohepatitis (NASH). Both of these patients were successfully treated surgically for a diagnosis of invasive breast cancer, and were transplanted at 7.6 months and 19 months after their breast cancer surgery.

Figure 1.

Figure 1.

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MELD-Na scores did not change significantly following breast cancer surgery.

Discussion

There exist no studies in the medical literature that examine outcomes among patients with both cirrhosis and early stage breast cancer. This is due to the general dogma of surgical nihilism which exists for cirrhotic patients and the relative infrequency of concomitant diagnoses. Early studies demonstrated a high mortality risk for surgery in patients with cirrhosis. Specifically, a 10, 30, and 82% mortality rate has been quoted in the literature for patients with Child-Pugh Class A, B, and C scores, respectively. (9–11) Notably, the patients in these particular studies underwent abdominal procedures rather than breast cancer surgery, which is less likely to elicit the same degree of stress response. Furthermore, the mortality estimated for patients with cirrhosis undergoing surgery have declined in the modern era given improved medical treatment of cirrhosis and less invasive surgical techniques. Concerns remain, however, that anesthesia itself may acutely worsen a patient’s hepatic reserve during surgery by altering the patterns of the hepatic and portal blood flow causing liver ischemia, thus placing the patient’s life at risk. (12) As a result of these concerns, breast cancer surgery has historically been avoided in this patient cohort. Early stage breast cancer management in patients with cirrhosis may also be deescalated because their liver disease appears to pose the largest immediate threat to their mortality. Finally, with a reported 5-year cumulative incidence of post-transplant malignancy greater than 4%, solid organ transplant recipients have an already elevated cancer risk compared to the general population. (13, 14) This risk is potentially even higher in patients with a pre-existing diagnosis of cancer. Thus, given the scarcity of organs available for transplantation, pre-existing extrahepatic cancer is often viewed as a contraindication for liver transplantation. (15, 16) To avoid operative risk if temporizing surgical care is warranted based on concomitant cirrhosis, these patients, all of whom had estrogen receptor (ER) positive disease could be managed with neoadjuvant endocrine therapy. To avoid risk of chemotherapy, such patients could instead safely receive adjuvant endocrine therapy.

Based on our experience operating on breast cancer patients with Child-Pugh Class A or B cirrhosis, we do not recommend contraindicating future liver transplantation because of a prior early stage breast cancer diagnosis if patients can complete recommended cancer directed therapies and are considered at low risk for recurrence by the treating oncology multidisciplinary team. Clinical risk assessment may include the Genomic Health Recurrence Score or traditional clinical risk stratifiers such as tumor size, grade, patient age, Ki67, and nodal status. Patients with early stage (Stage 0-I) breast cancers typically have excellent 5- and 10-year survival rates that approach 100%. (17, 18) Most of these patients are considered cured following multidisciplinary breast cancer treatment that includes surgery as well as adjuvant radiation, endocrine therapy, and chemotherapy when indicated. (18) Although the usual practice in many institutions is to delay transplantation for 2–5 years after a cancer diagnosis, the competing co-morbidity of end stage liver disease portends a more imminent threat to the patienťs life than a favorable biology ER positive breast cancer, which is predicted to have low rates of recurrence and can be managed with endocrine therapy for up to ten years. Therefore, our transplant program's philosophy was to consider early transplantation in breast cancer patients treated with intent to cure multidisciplinary treatment, inclusive of surgery. Without surgical treatment of their breast cancer, however, the patients with cirrhosis would not be offered a lifesaving organ transplantation, due to this existing untreated cancer, if their liver function deteriorates. Interestingly, no patients presented with locoregionally advanced or metastatic breast cancers concomitant with cirrhosis, likely since the pre-transplant population underwent annual screening mammography allowing for early detection of breast cancers.

Our series showed that breast surgery in the form of segmental mastectomy or total mastectomy and sentinel lymph node biopsy (SLNB) can be performed safely in patients with liver cirrhosis. These surgical procedures did not result in a statistically significant worsening of the patient’s liver disease as measured by MELD-Na. There were also no deaths in the immediate postoperative period in contrast to what was suggested by previous papers focusing on abdominal surgery in patients with cirrhosis. These patients also did not experience an increase in the rates of common breast surgery related complications such as seroma, hematoma, or surgical site infection as our patients did not experience any of these complications. (20) The postoperative complications which were experienced were related to their hepatic dysfunction and included thrombocytopenia and hepatic encephalopathy that resolved with standard treatment without requiring admission to the intensive care unit. The patients' hospital length of stay following breast cancer surgery was short despite the cirrhosis. The average length of hospitalization was 1.1 days of inpatient care. All patients were planned for hospital admission for observation given the elevated risks associated with the co-morbidity of cirrhosis.

While breast cancer is a heterogeneous disease with established intrinsic subtypes (21), all patients in our cohort had estrogen and progesterone receptor positive, and Her2-negative tumors. The expression of the estrogen receptor might not be a coincidence but rather an expected phenotype of breast cancer in this unique group of patients. According to case reports and epidemiologic studies, both men and women with alcoholic liver cirrhosis demonstrate abnormal metabolism of sex hormones causing a decrease in circulating androgens by increasing levels of sex hormone-binding globulin leading to an increase in the metabolism of estradiol to estrogen and a rise in estrogen levels. (22–24) There are also case reports describing male patients with liver cirrhosis but no known genetic mutations that predispose to breast cancer who have developed estrogen and progesterone receptor-positive breast carcinoma. (25–28) It is possible that estrogen receptor, progesterone receptor positive, human epidermal receptor 2-negative tumors were the most common breast cancer subtype in our patient cohort because this is the most predominant subtype of breast cancer and our cohort is small. However, it is also possible that this is the predominant subtype given the exposure to elevated estrogen levels that is common in this patient population. Patients with the estrogen receptor and progesterone receptor positive, human epidermal receptor 2-negative tumors have better outcomes than triple negative or human epidermal receptor 2-positive breast cancers. (29) While it is unknown what percentage of patients with cirrhosis would develop breast cancer, the rates of de novo malignancies after patients with cirrhosis undergo a liver transplantation is well documented. Over 20% of the patients status post liver transplant will develop de novo malignancies. (30) The patients in our cohort predominantly received aromatase inhibitors as adjuvant treatment. Tamoxifen was not frequently offered due to a risk of worsening hepatic function. (31, 32) Due to concerns regarding hepatotoxicity, tamoxifen might not be the best choice in breast cancer patients with a diagnosis of cirrhosis.

In examining diagnostic interventions and adjuvant therapies in these patients following surgery, it is recommended to consider balancing risk in relation to treatments that could contribute to clinical decompensation. (6) While recommendations exist to forego SLNB in populations with limited survival (33), all patients with invasive breast cancer in our cohort underwent SLNB because the transplant hepatologists requested axillary staging in order to appropriately risk stratify patients for consideration for transplant. Additionally, an OncotypeDx score was sent by the oncologic team on four out of the five patients seen at our institution who were diagnosed with an invasive, estrogen receptor positive, progesterone receptor positive, node negative breast cancer that was greater than 4 mm in size. The Oncotype was performed to risk stratify the patients and often proved that they had a low risk tumor biology. However, any adjuvant treatment based on the Oncotype score would need to be balanced with the assessment of the risks and benefits. In our cohort, while two patients had high-risk recurrence scores, no patients received chemotherapy. OncotypeDx is indicated to use to make a treatment decision for or against cytotoxic chemotherapy, however, use of chemotherapy is generally not appropriate in patients with cirrhosis since it could potentially result in worsening of their liver disease. It is interesting though that axillary staging and ordering of Oncotype was performed in almost all eligible patients to help identify those most likely to benefit from chemotherapy given that the Oncotype test is a prognostic as well as a predictive biomarker. (34) Genomic testing was used to help make the case that patients might be suitable transplant candidates given a finding of low risk tumor biology. Although this reflects the transplant’s team belief that estrogen receptor positive breast cancer overall has a relatively favorable prognosis and that such patients would benefit from an intention to cure, a prospective multi-institutional clinical registry with uniform inclusion criteria is warranted to generalize this approach and to determine if genomics may be an acceptable clinical predictor of favorable transplant candidates.

Five patients in this study who underwent lumpectomy received adjuvant radiation at our institution. The sixth patient treated with lumpectomy had a diagnosis of ductal carcinoma in situ (DCIS) and declined radiation therapy. Her DCIS recurrence score was sent and was noted to be low (0), translating to a 9% risk of any local recurrence, invasive or in situ, and a 3% risk of DCIS local recurrence.

All of our patients received adjuvant endocrine therapy. Most (87.5%) were treated with aromatase inhibitors instead of tamoxifen as discussed above, due to concerns of tamoxifen-induced hepatotoxicity in addition to an increased incidence in thromboembolism. (37) It is important to mention that this cohort of patients already has a higher risk of thromboembolic events due to malignancy diagnosis as well as liver dysfunction.

Despite these patients not being treated with maximal adjuvant therapy, we did not observe any breast cancer recurrences in this cohort of patients over the median 30.5 months of follow-up. Furthermore, while solid organ transplant recipients have an elevated five year cancer risk compared to the general public (14), we did not document any cases of breast cancer recurrence in the two patients who underwent liver transplantation. Finally, one patient died during the follow-up period, but this death was not in the immediate postoperative period, and was related to worsening hepatic dysfunction without transplantation more than 6 months after breast surgery.

We acknowledge that there exists significant selection bias in terms of which patients with concomitant breast cancer and cirrhosis were offered breast cancer surgery as part of multidisciplinary treatment with curative intent, inclusive of radiation therapy and endocrine therapy as appropriate. Clinicians selected patients who had favorable tumor subtypes, small overall tumor size and favorable liver disease with only Child A and B patients included.

Other limitations of our study include a small sample size, a single institution, retrospective study design, and less than five years of clinical follow-up time. Yet, our data set is unique and cannot be compared to previous studies because no previous publications cite the rate of breast cancer recurrence following solid organ transplantation, as patients with prior breast cancer diagnoses are frequently not offered transplantation.

Conclusions

Our data indicate that it may be safe and beneficial to operate on patients with hepatic dysfunction, including cirrhosis, and early stage breast cancer. The five and ten-year survival of patients with early stage breast cancer in the general population is known to be favorable, while survival of patients with cirrhosis and breast cancer has not been previously reported. Since cirrhosis may pose a greater threat to longevity than breast cancer, some physicians may be tempted to de-escalate breast cancer surgical care. Our series shows that surgical intervention for early stage breast cancer in cirrhotic patients does not result in hepatic decompensation based on the MELD-Na score, lengthy hospitalization, increased readmission, or death. Breast surgery can be safely offered in appropriately selected patients with cirrhosis and is compulsory for candidacy for future liver transplantation listing or solid organ transplantation should the hepatic dysfunction progress. Adjuvant therapies offered to this patient cohort were not standardized, though we recognize that studies utilized for counseling patients of recurrence risk and survival benefit may not apply to this group of patients and is nuanced based on individual risk factors. We advocate breast cancer surgery, endocrine and radiation therapy when indicated, with an attempt to achieve a curative intent, for patients with early stage breast cancer and Child-Pugh Class A and B cirrhosis as some of these patients will develop worsening liver dysfunction and, after breast cancer treatment, can be listed for life-saving liver transplantation. Epidemiological studies might add insight into the population-level incidence of breast surgery in cirrhotic populations, frequency of surgical intervention, and explore the potential risk to benefit ratio related to subsequent transplantation or complications secondary to liver failure.

Highlights.

Surgery can be safely employed in the breast cancer treatment of selected cirrhotic patients and is necessary for candidacy for future liver transplantation.

Acknowledgments

This project was supported in part by the USC Norris Core Grant from the National Cancer Institute (P30CA014089).

Footnotes

Disclosures

Dr. Lang is on the speaker bureau of Genomic Health and receives research funding from ANGLE Parsortix. All other authors declare that no potential conflicts of interests exist. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

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