Our study introduces the detailed process of CRS + HIPEC and demonstrates that patients with BC PC can benefit from the treatment. CRS + HIPEC extends OS of BC PC patients. There are no SAEs during CRS + HIPEC perioperative period.
The most common metastasis sites of primary BC with invasive ductal carcinoma (IDC) include regional lymph nodes, lung, liver, bones, brain, and skin. BC with invasive lobular carcinoma (ILC) frequently affects bones, retroperitoneum, peritoneum, gynaecological organs, and gastrointestinal (GI) tract [15–16]. ILC accounts for less than 10% of all BCs and ICD accounts for more than 90%. However, the loss of E-cadherin expression on the surface of tumor cells in ILC patients leads to more diverse forms of metastasis. It prevents cell adhesion and promotes tumor cell migration [17]. Peritoneal metastasis can be diagnosed by CT or surgery. IDC patients account for only 3% while ILC patients account for 11% (P = 0.006). Regardless of IDC or ILC, PC is an important reason of morbidity and mortality [18]. In our study, there were 1 patient with ILC and 3 patients with IDC of the primary BC (Fig. 2–4). The metastasis tumor and the primary tumor had the same pathological type.
The prognosis of PC showed poor survival than other regional metastases from BC. The median survival time was 20.5 months from diagnosis of metastasis BC while the median survival of patients with BC PC was only 1.5 months [19]. Another study showed the OS was 5.8 months in patients with BC PC from the metastasis PC was diagnosed as compared to 22.6 months in patients with no metastasis PC. Patients with synchronous metastases have significantly better survival than those with metachronous metastases [20]. There were 2 cases with metachronous metastases and 2 cases with synchronous metastases in our study. The OS of the synchronous metastases’ patients had reached 28 months and the longest OS of the metachronous metastases had reached 52 months to March 2020.
BC PC caused abdominal distension, abdominal pain or severe intestinal obstruction. And all patients in our study had at least one of the above symptoms. However, there were no effective treatments to relieve these symptoms and chronic malnutrition caused poor prognosis. The traditional treatment methods for BC PC were chemotherapy or radiotherapy but the effect of the treatment was unsatisfactory. The treatment of BC PC in our study was CRS + HIPEC combined with chemotherapy. To achieve radical CRS, the median number of resected organs were 7 and 2 patients reached CC 0. The tolerance to hyperthermia was higher in normal tissue than the tumor tissue. HIPEC could prevent the adhesion postoperatively, as well as decrease the accelerative effect of healing on tumor cell entrapment by killing the granulocytes and monocytes. The synergistic anti-cancer effect could be dramatically increased at 43℃. Hyperthermia could increase the response rates of cancer cells to HIPEC drugs, and the depth of HIPEC drugs into the tumor tissues. At last, loosening the adhesion of the intestine or ileostomy could relieve the intestinal obstruction. In our study, one case underwent loosening the adhesion of the intestine, and another underwent ileostomy, the abdominal distension or bowel obstruction of which relieved completely. All patients in our study received adjuvant chemotherapy and endocrine therapy pre- and post-CRS + HIPEC. The average OS reached 32 months better than literature [4].
Estrogen played an important role in the occurrence and prognosis of BC. The estrogen receptor (ER) was one of the important biomarkers to predict the prognosis of BC [21]. BC patients with ER- and progesterone receptor (PR)- positive had a better prognosis [22]. Human epidermal growth factor receptor 2 (HER-2) regulates cell proliferation, growth, and survival. HER-2 was a transmembrane tyrosine kinase receptor [23–24]. BC patients with high levels Ki-67 usually have a poor prognosis due to Ki-67 was a nuclear proliferation marker [25]. In our study, two patients with synchronous BC PC, one with Ki-67 80–90% and another with HER-2 positive, maybe one of the reasons for the early peritoneal metastasis. The other two cases received standard adjuvant therapy after the primary lesion. All patients received tamoxifen treatment for 5 years and metastasis occurred after 5 years of discontinuation (all 4 cases had positive estrogen receptors). It was necessary to receive estrogen therapy for hormone receptor-positive BC PC patients after CRS + HIPEC. At present, all the 4 patients had received letrozole orally after CRS + HIPEC and chemotherapy. No tumor progression occurred at the time of follow-up.
The average PCI was 29.5, which heralded the difficulty of CRS. The average operation duration was 8.8 h and average 7 organs were resected. The average blood loss was 525 ml and the average ascites volume was 3,625 ml. While there were no SAEs during the perioperative period and the average hospital stay was 15 d. The safety of CRS + HIPEC was accepted. It was important that a professional PC treatment team implemented standardised CRS + HIPEC. Otherwise, you maybe come to the opposite conclusion that CRS + HIPEC was not the treatment of choice [26]. This article provided new ideas and methods for the treatment of BC PC patients. This finding merits further investigation in larger studies.
The disadvantage of this study was that the number of patients was too small to perform statistical analysis. The follow-up time was short, no comparison with a control group and lack of questionnaires to evaluate quality of life (QoL). Therefore, these findings in this study required more confirmations from a large sample of evidence.