What is a systemic therapy?  

Systemic therapies are therapies meant to inhibit cancer growth throughout the body, rather than solely in the breast. Systemic therapies are the main treatment for stage IV breast cancers that have already spread, and are also used to prevent stage I, II, or III cancers from recurring after surgery or to prevent in situ cancers from becoming invasive.

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Targeted therapies tre cancer throughout the body. There are different targeted therapies based on the proteins/receptors that your cancer cells express: HER2 targeted therapies, Hormone Receptor + targeted therapies, and triple negative breast cancer (TNBC) targeted therapies. 

HER2 Targeted Therapies
HER2 targeted therapies are therapies that target the HER2 protein on the surface of HER2 positive breast cancer cells. HER2 is a protein that, when activated, yields a downstream path that signals cancer cells to divide. By targeting HER2, cancer cells no longer receive this signal, and therefore will no longer divide.

There are three main types of HER2 Targeted Therapies:

Monoclonal Antibodies: Monoclonal antibodies are lab made antibodies. Antibodies are proteins made by the immune system that recognize and remove dangerous substances from the body. Therefore, monoclonal antibodies are engineered to recognize and attach to HER2 on the surface of cancer cells and stop them from growing and dividing. ex: traztuzamab and pertuzamab
Antibody Drug Conjugates:  These drugs consist of a monoclonal antibody bonded to a chemo drug; the monoclonal antibody finds the HER2, and the chemo kills the cancer cells. Ex: kadcycla and enhertu
Kinase Inhibitors: HER2 is a protein called a kinase that, when activated, yields a downstream path that signals cancer cells to divide. Kinase inhibitors block HER2, therefore inhibiting cancer growth and division, as the HER2 receptors on the cancer cells have nothing to attach to. Ex: Neratinib (Nerlynx) and Tucatinib (Tuckysa)

Side Effects of HER2 Targeted Therapies 
*Pregnant women should not take HER2 targeted therapies*
These side effects are uncommon, but possible. 

• heart damage or failure (antibody drug conjugates and monoclonal antibodies): those with underlying heart issues or at high risk for heart issues are at higher risk; furthermore, coupling these drugs with chemo drugs with a cardiotoxicity risk also heightens the risk of heart damage or failure.

• severe diarrhea (monoclonal antibodies)  

• lung disease (enhertu) 

• liver issues (kinase inhibitors) 

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Targeted Therapies for Triple Negative Breast Cancer (TNBC)​
Triple Negative Breast Cancers are those which are ER, PR, and HER2 negative, meaning that neither hormone therapy or HER2 targeted therapies can fight TNBC.

However, chemotherapy, coupled with an antibody drug conjugate directed at a specific protein present in TNBC, can fight the spread of triple negative breast cancer. 
Monoclonal antibodies are lab made antibodies. Antibodies are proteins made by the immune system that recognize and remove dangerous substances from the body.  Antibody drug conjugates consist of a monoclonal antibody bonded to a chemo drug; the monoclonal antibody finds the cancer cells, and the chemo kills the cancer cells. 

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Trodelvy (the antibody drug conjugate used to treat TNBC) is engineered to find Trop 2, a protein on the surface of breast cancer cells that fuels their growth, and the chemotherapy can then kill the cancer cells.
​Trodelvy is usually used a third line treatment for TNBC (after two rounds of chemo).

Trodelvy can also be used in HR+ breast cancers after hormone therapy stops working.  
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Side Effects of Trodelvy: 

• vomiting, diarrhea

• fatigue

• appetite changes 

• anemia (low red blood cell count) 

• increased infection risk 

• infusion reaction 

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Targeted Therapies for HR (Hormone Receptor) Positive Breast Cancers 
These targeted therapies are designed for those who have ER/PR positive breast cancers. They are often given in combination with aromatase inhibitors. 

CDK4/6 Inhibitors 
These drugs work by blocking proteins called CDK's that HR+ breast cancers express. This inhibits cancer growth and division. 
Ex: Ribociclib (kisquali) and Palbociclib (Ibrance)
Who can possibly use CD4/6 Inhibitors? 
-women with HR+ cancer that have gone through menopause (or have been put into menopause with ovarian suppression) (given with a Aromatase inhibitor) 
-women who have already been through hormone/chemotherapy (cancer has mutated and become resistant) 
-women may take CDK4/6 inhibitors along with hormone therapy after breast cancer surgery to reduce recurrence risk
Possible Side Effects of CDK 4/6 Inhibitors
-anemia (low red blood cell count) 
-increased risk of infection (low white blood cell count) 
-fatigue
-vomiting, nausea, diarrhea
-very rare: pneumonitis (lung disease)
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P13K Inhibitor (Piqray/Alpelisib)  
Piqray blocks a protein called P13K that HR+ breast cancer express, inhibiting cancer division + growth. 
Who can possibly use Piqray? 
-women with advanced HR+ breast cancer who have become resistant to an aromatase inhibitor (their cancer has a P13KCA mutation + therefore has developed the P13K protein).
Possible Side Effects
-hyperglycemia (high blood sugar) 
-rash
-diarrhea
-loss of appetite 
-higher infection risk 
-kidney issues
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mTOR Inhibitor (Everolimus/Afinitor) 
-This inhibitor blocks mTOR, a protein expressed in cancer cells that is involved with cancer growth. 
Who Can Possibly Take Afinitor? 
-Afinitor is often used in combination with the aromatase inhibitor aromacin or the hormone therapy fulvesterant. It is usually used after a woman has become resistant to first line aromatase inhibtors. 
Side Effects 
-higher infection risk (low white blood cells) 
-anemia (low white blood cells) 
-mouth sores 
-low appetite 
-hyperglycemia (high blood sugar) 
-high cholesterol
-fatigue and weakness
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AKT Inhibitor (Truquab/Capivasertib) ​
Truquab works by blocking  AKT, a protein in breast cancer cells that helps them grow and divide.
Who could possibly use this drug? 
Truquab is for those with advanced HR+ HER2- breast cancers. It can only be used if breast cancers cells have one of three specific mutations and if they have become resistant to hormone therapy. 
Side Effects: 
-severe diarrhea (most common side effect) 
-hyperglycemia (high blood sugar) 
-increase infection risk (low white blood cells ) 
-anemia (low red blood cells) 
-mouth sores
-fatique
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Sacituzumab govitecan (trodelvy) 
Trodelvy is a type of antibody drug conjugate. 
Antibody drug conjugates consist of a monoclonal antibody bonded to a chemo drug. The monoclonal antibody finds the cancer cells, and the chemo kills the cancer cells. Trodelvy is engineered to find Trop 2, a protein on the surface of breast cancer cells that fuels their growth, and the chemotherapy can then kill the cancer cells.
Who can possibly use trodelvy? 
Those with advanced HR+ (or TNBC) breast cancers who have been through two different chemotherapies and hormone therapy may be eligible for this drug. 
Possible Side Effects of Trodelvy: 
-higher infection risk (low white blood cell counts) 
-anemia (low red blood cell counts) 
-fatigue
-nausea, diarrhea, vomiting 
-low appetite 
-rash