Breast Cancer Palliative Care





Breast cancer is an incredibly complex disease, and when metastatic or terminal, it becomes even more complex. The difficulties clinicians encounter with this disease go far beyond the malignancy. It includes, in many cases, particularly young women, families, including children directly affected by the disease. The course and management in these complex situations start with therapy directed at the breast cancer, although this also includes symptom management, psychosocial issues, spiritual domains, and goals of care. Many of these are addressed by the palliative care team, although this may include other ancillary personnel such as alternative medicine practitioners, dietitians, and counselors.


Palliative Chemotherapy


The goal of palliative chemotherapy is often to improve overall survival. Median overall survival is now more than 3 years among metastatic breast cancer patients, and ranges from a few months to years. Palliative care is imperative in the management of metastatic breast cancer, including improved quality of life, alleviation of symptoms, and management of side effects to the treatment.


Treatment selection is based on clinical factors, tumor biology, and goals of care, and treatment may include systemic chemotherapy, endocrine therapy, biologic therapy, and supportive care measures. The most important predictors of treatment response are hormone receptor status and HER2/neu overexpression. Patients with genetic alterations in breast cancer susceptibility genes 1 or 2 (BRCA) are more likely to respond to poly(ADP ribose) polymerase (PARP) inhibitors. Regarding chemotherapy, consistent predictors of poor response are progression with prior chemotherapy for advanced disease, relapse within 12 months of adjuvant chemotherapy, poor performance status, and multiple disease sites including visceral disease.


Pathways create a standardized approach to the care of our patients. The National Comprehensive Cancer Network provides multiple options for the treatment of patients. Unlike the NCCN, other pathway systems provide a more standardized approach and allow medicine an enormous potential to harvest retrievable data and influence the future care of patients. ( Tables 14.1 to 14.5 ).



Table 14.1

HER2/neu-Negative Postmenopausal or Premenopausal Receiving Ovarian Ablation or Suppression











Aromatase inhibitor + CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib)
Everolimus plus endocrine therapy
Selective estrogen receptor downregulator (fulvestrant) plus a nonsteroidal aromatase inhibitor (letrozole, anastrazole)
Fulvestrant plus CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib)


Table 14.2

HER2/neu-Positive Postmenopausal or Premenopausal Receiving Ovarian Ablation or Suppression













Aromatase inhibitor ± trastuzumab
Aromatase inhibitor ± lapatinib
Aromatase inhibitor ± lapatinib + trastuzumab
Fulvestrant ± trastuzumab
Tamoxifen ± trastuzumab


Table 14.3

HER2/neu-Negative Chemotherapy















Anthracyclines (doxorubicin, liposomal doxorubicin) a
Taxanes (paclitaxel) a
Antimetabolites (capecitabine, gemcitabine) a
Microtubule inhibitors (vinorelbine, eribulin) a
Sacituzumab govitecan a
Other regimens (cyclophosphamide, docetaxel, albumin-bound paclitaxel, epirubicin, ixabepilone) a


a Combinations useful in certain circumstances.



Table 14.4

HER2/neu-Positive Chemotherapy







































First line Pertuzumab + trastuzumab + docetaxel
Pertuzumab + trastuzumab + paclitaxel
Second line Fam-trastuzumab deruxtecan-nxki
Ado-trastuzumab emtansine (T-DM1)
Third line Tucatinib + trastuzumab + capecitabine
Trastuzumab + docetaxel or vinorelbine
Trastuzumab + paclitaxel ± carboplatin
Capecitabine + trastuzumab or lapatinib
Trastuzumab + lapatinib (without cytotoxic therapy)
Trastuzumab + other agents
Neratinib + capecitabine
Margetuximab-cmkb + chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine)


Table 14.5

Biomarker-Associated and Molecular Testing a







































Breast Cancer Subtype Biomarker Detection US FDA-Approved Agents
Any


  • BRCA1 mutation



  • BRCA2 mutation

Germline sequencing


  • Olaparib



  • Talazoparib

HR-positive/Her2-negative PIK3CA- activating mutation PCR (blood or tissue block if blood negative), molecular panel testing Alpelisib + fulvestrant
TNBC PD-L1 expression (Threshold for positivity combine score of ≥10) IHC Pembrolizumab + chemotherapy (albumin-bound paclitaxel, paclitaxel, or gemcitabine and carboplatin)
Any NTRK fusion FISH, NGS, PCR (tissue block)


  • Larotrectinib



  • Entrectinib

Any MSI-H/dMMR IHC, PCR (tissue block)


  • Pembrolizumab



  • Dostarlimab-gxly

Any TMB-H (≥10 mut/mb) NGS Pembrolizumab

dMMR , Deficient DNA mismatch repair; FISH , fluorescence in situ hybridization; IHC , immunohistochemistry; MSI-H , microsatellite instability-high; NGS , next-generation sequencing; NTRK , neurotrophic tyrosine receptor kinase; PCR , polymerase chain reaction; PD-L1 , Programmed cell-death ligand 1; TMB-H , tumor mutational burden-high.

a Biomarkers associated with US FDA-approved therapies.



Symptom Management


The most important component of palliative management is symptom management.



  • •

    Pain




    • Nonpharmacologic




      • The idea of mind and body healing has been around for decades. How these enter symptom management varies, typically by patient.



      • Rehabilitative physical modalities include ultrasound, therapeutic exercise, occupational therapy, hydrotherapy, therapy for specific disorders such as lymphedema, and heat and cold therapies.



      • Psychological therapies include psychoeducation interventions, cognitive behavioral therapy, relaxation therapy, guided imagery, other types of stress management, hypnotherapy, and other forms of psychotherapy.



      • Neurostimulation includes implanted neurostimulators, both transcutaneous and transcranial.



      • Additional complementary therapies include acupuncture, massage, physical/movement (e.g., yoga), music therapy, art therapy, and other ideas such as mind occupational therapy (cognitive exercises such as coloring books or games such as sudoku).





  • Pharmacologic




    • Nonopioid




      • Treatment of cancer-related pain typically incorporates a pyramid strategy. Pain control with nonopioid measures is encouraged prior to consideration of opioids.



      • Nonopioid medications include acetaminophen, nonsteroidal anti-inflammatory drugs, topical agents, antidepressants, anticonvulsants, oral local anesthetics, steroids, cannabinoids, alpha-2 agonists, and ketamine.



      • Interventional therapies include nerve blocks, spinal analgesics, and surgical neuroablation.



      • Opioid



      • Opioids remain an integral part of the management of pain in terminally ill cancer patients. The difficulties with opioids are the serious nature of the addiction issues surrounding these medications, and as a result, these medications are heavily regulated.



      • We continue to encourage the use of opioids in situations where nonopioid measures fail to gain adequate pain control.




  • •

    Nausea/vomiting




    • Although nausea and vomiting continue to be important to control clinically, many patients receive adequate coverage with standard premedication for their chemotherapy.



    • Antiemetic medications are classified based on drug type ( Table 14.6 ).



      Table 14.6

      Classification of Antiemetic Medications

























































      Prokinetic agents Metoclopramide
      Antihistamines Diphenhydramine
      Hydroxyzine
      Promethazine
      Dopamine agonists Haloperidol
      Chlorpromazine
      Prochlorperazine
      Olanzapine
      Serotonin 5HT3 receptor antagonists Ondansetron
      Granisetron
      Neurokinin receptor antagonists Aprepitant
      Benzodiazepine Diazepam
      Lorazepam
      Corticosteroids Dexamethasone
      Prednisone
      Cannabinoids Dronabinol
      Other anticholinergics Scopolamine
      Hydrobromide



    • Each class of drug type functions better depending on the nausea that is induced. Prokinetic agents are primarily used for gastric stasis and gastrointestinal dysmotility from various causes. Antihistamines are useful for vestibular and gut receptor nausea and vomiting. They are relatively contraindicated for constipation because they may further slow the bowel. Dopaminergic agents are best used for medication- and metabolic-related nausea. Serotonin 5-HTZ receptor antagonists are used for postoperative and radiation- and chemotherapy-induced nausea. Neurokinin receptor antagonists are particularly helpful for delayed chemotherapy-induced nausea and vomiting. Benzodiazepines are useful for anticipatory or anxiety-provoked nausea. Corticosteroids are useful for hepatic capsular distension, anorexia, and increased intracranial pressure. Cannabinoids help with chemotherapy-induced nausea and vomiting. Other anticholinergics are used for motion- or movement-related nausea and vomiting.



    • Gabapentinoids (gabapentin and pregabalin) have been used successfully for neuropathic pain. A summary of the benefits of gabapentinoids was published in 2015. It showed improvement (50% reduction in pain intensity) for gabapentin when treating postherpetic neuralgia. The number needed to treat to harm a single patient was 25.6, demonstrating a wide therapeutic index, and gabapentin has been successfully used for cancer-related pain. It does appear that if pain does not respond to one gabapentinoid, it can respond to the alternative gabapentinoid.



    • Analgesic antidepressants have also been widely studied for varied types of chronic pain. Duloxetine is often used in conjunction with gabapentinoids and appears to be a more powerful pain medication as an alternative to opioids in cancer-related pain. It is common for duloxetine or a similar antidepressant to be used in combination with gabapentinoids for adequate cancer-related pain control.




  • Opioids


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Apr 6, 2024 | Posted by in ONCOLOGY | Comments Off on Breast Cancer Palliative Care

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