Abstract
The benefit of home parenteral nutrition (HPN) for patients with malnutrition due to peritoneal metastasis depends on the type of cancer. During the period 1999–2020, we treated 460 patients with metastatic and stage 4 breast cancer, 23 of whom were invasive lobular carcinoma (ILC). Of the 23 patients with ILC, 13 (57%) developed peritoneal metastasis, and 11 died of progression of peritoneal metastasis. Among these 11 patients, 2 patients who underwent surgery due to bowel obstruction, had no improvement, and died 1–4 months after surgery. The prognosis of the other 7 patients under BSC alone was poor, survival time were ranging from 1 to 5 months. The remaining two patients who were able to continue outpatient chemotherapy under HPN were able to prolong their survival time by 18 months and 26 months, respectively. We need to recognize that HPN and chemotherapy may prolong survival time in patients with peritoneal metastasis of ILC, and determine the indication for HPN based on the non-peritoneal life-threatening metastasis, length of treatment, availability of support for HPN management and outpatient chemotherapy, and the patient's willingness to accept it.
Keywords: Peritoneal metastasis, Home parenteral nutrition, Invasive lobular carcinoma
Introduction
Breast cancer is the most frequent malignant neoplasm in women, with 93,858 cases per year in Japan (2018). The survival rate is good, with a 5-year survival rate of 92.3%, but the number of deaths is the fifth highest after colorectal cancer, lung cancer, pancreatic cancer, and gastric cancer. In Japan, 14,839 (2019) people die annually from breast cancer [1].
The survival time after recurrence has been prolonged by advances in molecular targeted drugs and chemotherapeutic agents [2]. However, it is difficult to achieve a cure; therefore, the goal of treatment in recurrent breast cancer is to maintain quality of life (QOL) and to prolong the survival time [3, 4]. In patients with recurrent breast cancer, it is necessary to select a treatment based on the patient's QOL, predicted from the disease status and the expected effect on the survival.
Therapeutic agents for breast cancer are given according to the guidelines for each subtype [5, 6]. On the other hand, selection of therapeutic agents by histopathological type is rarely mentioned. Although, we reported that peritoneal metastasis develops at a high rate as a recurrence in invasive lobular carcinoma (ILC) and is a cause of death [7]. So far, no report has been seen that examines the therapeutic measures for peritoneal metastasis of breast cancer.
We reviewed the cases over a period of more than 20 years at a single institution, and the treatment options for patients with bowel obstruction due to peritoneal metastasis. Through this article, we report the usefulness and indications of home parenteral nutrition (HPN) and chemotherapy.
Case presentation
During the period 1999–2020, we treated 460 patients with metastatic and stage 4 breast cancer. Of these, 23 had ILC and the other 414 had invasive ductal carcinoma, 10 metaplastic carcinoma and 13 others (Fig. 1). Of the 23 ILC patients, 13 (57%) developed peritoneal metastases, and 11 died of worsening peritoneal metastases. Of the remaining two patients, one died of carcinomatous meningitis and one is currently being treated with hormonal therapy (Fig. 1).
Fig. 1.
Flow chart of patients who died of peritoneal metastasis
The DFI of the 11 patients who died of peritoneal metastasis was 41 ± 31 months, and the survival after recurrence and survival after peritoneal recurrence was 47 ± 38 months, and 27 ± 18 months, respectively (Table 1). All patients died due to difficulty in food intake and treatment as the disease progressed. As a result, two patients underwent surgery, but their bowel obstruction did not improve and died 1–4 months after surgery (cases 1 and 3). After food intake became difficult, the survival time in the 7 cases of BSC alone was 1–5 months. Altogether, the survival time after inability to take food was 6 ± 8 months. Among them, two cases were treated with HPN and chemotherapy to prolong their survival time (cases 4 and 8) (Table 1).
Table 1.
Clinical course after recurrence of 11 patients who died of peritoneal metastasis
| No of Pt | DFI including adjuvant therapies | Months under each therapies after relapse | Survival after relapse | Survival after diagnosis of peritoneal metastasis | Survival after bowel obstruction | Treatment after bowel obstruction | |||
|---|---|---|---|---|---|---|---|---|---|
| Hormone therapy | CDK4/6 inhibitor | Chemotherapy | BSC | ||||||
| 1 | 35 | 0 | 0 | 0 | 5 | 5 | 5 | 4 | surgery |
| 2 | 0 | 3 | 0 | 0 | 15 | 18 | 18 | 3 | BSC |
| 3 | 57 | 2 | 4 | 8 | 4 | 18 | 2 | 1 | surgery |
| 4 | 80 | 0 | 0 | 23 | 2 | 25 | 25 | 18 | HPN + + chemo |
| 5 | 56 | 0 | 0 | 20 | 14 | 34 | 34 | 2 | BSC |
| 6 | 0 | 24 | 0 | 10 | 5 | 39 | 5 | 5 | BSC |
| 7 | 0 | 24 | 0 | 13 | 4 | 41 | 41 | 1 | BSC |
| 8 | 66 | 2 | 0 | 47 | 2 | 51 | 51 | 26 | HPN + + chemo |
| 9 | 38 | 5 | 1 | 53 | 2 | 61 | 61 | 2 | BSC |
| 10 | 83 | 53 | 0 | 27 | 11 | 91 | 22 | 1 | BSC |
| 11 | 35 | 59 | 0 | 74 | 3 | 136 | 36 | 2.3 | BSC |
| Mean ± SD (months) | 41 ± 31 | 16 ± 22 | 0.5 ± 1.2 | 25 ± 27 | 6 ± 5 | 47 ± 38 | 27 ± 18 | 6 ± 8 | na |
DFI Disease-free interval, BSC Best supportive care, HPN Home parenteral nutrition
Case 4: A 62-year-old woman. At the age of 54, she underwent breast-conserving therapy for left breast cancer. The pathological findings of the resected specimen were ILC, T2n2 (4/18), M0, stage 2b and ER8 + PR0Her20 on immunohistochemistry. The patient was treated with postoperative chemotherapy (EC-DTX), radiation and hormone therapy (Fig. 2). At the age of 60 (6 years after surgery), she underwent appendectomy, and subsequently had subileus symptoms and was diagnosed as peritoneal metastasis from endoscopic biopsy from the nodules in the colon (Fig. 3A). She was treated with chemotherapy, but her condition gradually worsened to subileus. At that time, we considered the indication for surgery, but PET scan showed extensive peritoneal dissemination (Fig. 3B), and judged that the effect of surgery could not be expected. HPN was started and outpatient chemotherapy was continued, which prolonged the patient's survival time by 18 months. During the treatment period, the patient was able to drink fluids and was given HPN 1000 Cal during the night-time. She was administered 14 cycles of elibrin and 3 cycle of bevacizumab + weekly paclitaxel, consequently, prolong the life-time for 18 months.
Fig. 2.
Clinical course of case 4. EC epirubicin cyclophosphamide, DTX docetaxel Tor toremifene, LET Letrozole, Rad radiation, Bvp bevacizumab paclitaxel
Fig. 3.
Endoscopic finding and Positron Emission Tomography (PET) of case 4. Endoscopic finding of the colon fiberscope indicated nodules of cecum (3A), and PET revealed ascites and mild accumulation of Fluorodeoxy-glucose (FDG) in whole abdomen (3B) indicating carcinomatous dissemination.
Case 8: A 67-year-old woman underwent a right mastectomy at the age of 57. Pathological examination of the surgical specimen revealed ILC, T3n1 (1/15), ER7 + PR-Her20. The patient was treated with postoperative chemotherapy (EC-DTX), and hormone therapy (Fig. 4). At the age of 65 (7 years after surgery), she developed stenosis of the pyrolus and bile duct (Fig. 5A, B), and biopsy of the gastric wall revealed metastasis of ILC. After 25 months of chemotherapy, the patient had difficulty to eat. By her request, HPN was started and outpatient chemotherapy was continued. She was administered 14 cycles of elibrin and 12 cycles of Bevacizumab + weekly paclitaxel, resulting in an additional 26 months of survival. The dosage of 1000–1500 Cal/day was continued. The patient occasionally complained of distress from not being able to eat, but stated that it was tolerable.
Fig. 4.
Clinical course of case 8. NAC neoadjuvant chemotherapy. Bvp bevacizumab paclitaxel, Cap capecitabine
Fig. 5.
CT and endoscopic finding of case 8. CT revealed the recurrent tumor surrounding the duodenum (5A) and pyloric stenosis with gastric nodules indicated metastasis of ILC (5B)
The experience of these two cases suggests that even in the situation of subileus, the continuation of HPN and chemotherapy may contribute to prolongation of survival time instead of choosing palliative surgery.
Discussions
Home parenteral nutrition (HPN) has become an essential technique for maintaining nutrition in patients with short bowel syndrome or intestinal obstruction who cannot receive enteral nutrition. However, the decision to perform HPN in the setting of peritoneal metastasis of cancer is often difficult to make. In each case, the decision should be based on whether it prolongs survival, improves QOL, and is costly and burdensome to caregivers [8–10]. In actual individual cases, it is appropriate to consider each situation and make a decision based on the patient's wishes.
Among various cancers, the utility of HPN has been reported in ovarian cancer [11]. Ovarian cancer is often accompanied by bowel obstruction due to cancerous peritonitis at an early stage, and improving the malnutrition state often improves the general condition and prolongs life. Furthermore, when chemotherapy is available, some patients survive beyond two years [12], which is considered significant.
Invasive lobular carcinoma of the breast is associated with a high rate of peritoneal dissemination in the late stage of recurrence [7, 13]. When peritoneal metastasis leads to intestinal obstruction, it is difficult to prolong life. However, peritoneal metastasis of ILC is similar to peritoneal dissemination of ovarian cancer, i.e., it is chemosensitive and metastases in other organs are not life-threatening. We performed HPN and continued chemotherapy in two patients and were able to extend their survivals for 18 months and 26 months, respectively.
These two patients had burdens such as inability to eat and restrictions on going out, but HPN improved their nutritional status and abdominal symptoms such as abdominal pain and vomiting. Both patients understood the significance of chemotherapy and attended for treatment without mental disability. They were able to spend in home more than one year, as playing their roles in the family. The support of the family and the visiting nurse who administered the HPN was essential to keep these situations. It has been reported that anxiety and depression improve after 1–3 months of HPN introduction [14]. We believe that the recovery of frailty associated with the improvement of nutritional status, contributes to the improvement of QOL.
In our 11 cases, peritoneal metastases were often difficult to diagnose, and the stage of progression at the time of diagnosis ranges from mid- to late stage of recurrence. And the mean survival time after diagnosis of peritoneal metastasis was 27 ± 18 months with wide range of 2–61 months. Therefore, we cannot uniformly state the pros and cons of HPN. However, the two cases reported here indicate that if HPN and chemotherapy can be continued, survival of more than 2 years can be expected. Although there are no randomized controlled clinical trials examining whether HPN should be used in patients with incurable cancer, the ESPEN guideline indicates that HPN can prolong life for 6 months in patients who are unable to eat and is useful for continuing chemotherapy [15]. If chemotherapy is expected to be effective, HPN and chemotherapy are considered to have an additive effect.
In addition, metastasis to multiple organs is also related to the worsening of the disease. In many cases, liver metastasis, bone metastasis, brain metastasis, etc. are involved, and even if nutritional disturbance is improved by HPN, survival cannot be extended, especially when liver metastasis and brain metastasis are life-threatening. In these cases, HPN may even decrease QOL, and best support care (BSC) is preferred. This is because the goal of treatment for recurrent breast cancer is to prolong life-time maintaining QOL.
In conclusion, we need to recognize that drug therapy can prolong life in cases of peritoneal metastasis of ILC, and it is important to determine the indication for HPN based on the individual patient's life-threatening metastasis other than peritoneal metastasis, duration of treatment, caregivers who support HPN management at home and outpatient chemotherapy, and the patient's willingness.
Author contributions
MI, HN, and AY contributed to writing the manuscript.TO, YH, AY, TE, and HW, served as attending physicians of the present patients. All authors read and approved the final manuscript.
Declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent
Information about this study is made public, and patients are guaranteed to refuse to participate. And written informed consents were obtained from patients of cases 4 and 8 concerning the publication of their clinical and genomic information.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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