Breast Cancer

Question 1

What SSRIs should be avoided with Tamoxifen and what is the impact of this?

Answer 1

Fluoxetine and Paroxetine. These meds can decrease the level of Tamoxifen.

Question 2

Which SSSRI should a patient be switched to if taking Tamoxifen?

Answer 2

Velafaxine and Citalopram

Question 3

For those who are intolerant of AIs what is the best next step? Name the category 1 recommendation in terms of how long they should be on the agent and the alternative

Answer 3

The category 1 recommendation is Tamoxifen for 5 years but the alternative is for 10 years but this option does not have a category 1 recc

Question 4

For those patients with early stage breast cancer who have 4 or more positive nodes how long should they be on endocrine treatment? For those with 3 or less?

Answer 4

They should receive extended duration treatment so beyond 5 years up to 10 years. For those with 3 or less you can use the BCI tool to determine if they would benefit from extended endocrine therapy.

Question 5

When deciding what patients with early stage breast cancer need chemotherapy, what is the tumor size cutoff? What is the exception with both HR+ and TNBC?

Answer 5

Any tumor less than or equal to 0.5cm does not require chemo. If there is micro mets to a lymph node (2 or less mm tumor present) these patients should receive chemo.

Question 6

For any early stage HER2+ patient, what is the preferred treatment? When is it preferred to add Pertuzumab?

Answer 6

Regardless of tumor size, every patient will need adjuvant chemotherapy plus Trastuzumab. If they have pN1 disease (greater than 2mm) then you add Pertuzumab to Trastuzumab.

Question 7

When giving chemo for T1a node neg HER2+ disease, what is the preferred regimen in the adjuvant setting and what is the category recommendation per NCCN? In the study that looked at this regimen up to what tumor size did they look at?

Answer 7

So the APT trial showed that for tumors that are node negative up to 3 cm in size patients have good survival outcomes with adjuvant weekly Paclitaxel with Trastuzumab. This is the recommended regimen, so this include T1 and T2 tumors (T2: 2-5 cm).

Question 8

For those who are postmenopausal with HR+ disease and need adjuvant therapy, what number of lymph nodes being positive negates doing oncotype and giving them chemo?

Answer 8

Those with 4 or more ipsilateral lymph nodes (pN2 or pN3).

Question 8

For post-menopausal patients who have undergone surgery for HR+ disease, what patients require chemo?

Answer 8

For those tumors greater than 0.5cm, those with tumors less than 0.5cm with micro mets (2mm or less), PN0, or PN1-3 and who have a oncotype score of 26 or higher. Also if the test was not done or the patient declined the oncotype score, then they should get chemo also.

Question 9

What does the NCCN guidelines say for premenopausal patients with HR+ early stage disease with node positive or negative disease and who needs chemo?

Answer 9

So for tumors greater than 0.5cm and a oncotype score less than or equal to 15 the cat 1 recc is adjuvant endocrine +/- OFS. For a oncotype score of 16-25 you can do adjuvant endocrine +/- OFS or you can do chemo w/adjuvant endocrine +/- OFS. Those with a score>25 (26 or higher) will need chemo in addition to endocrine and +/- OFS.

Question 10

For those early stage HR+ premenopausal patients who did not get a oncotype score done what is the cat 1 recommendation?

Answer 10

Adjuvant chemo with adjuvant endocrine therapy +/- OFS. It says another rec is just to give adjuvant endocrine and OFS.

Question 11

What is the recommendation for adjuvant therapy in premenopausal patients who have HR+ node positive disease?

Answer 11

All of these patients still need a oncotype. But it says in NCCN those with 1-3 nodes can get either chemo with endocrine and OFS or you can do endocrine and OFS alone. For those with 4 or more nodes they need chemo. A very high RS, these patients should get chemo (>25).

Question 12

Per NCCN Guidelines, for those patients with early stage HER2+ disease what chemo can you give and specifically what T/N stage?

Answer 12

For those patients with tumors up to 2cm. NCCN says you can give Weekly Paclitaxel with Trastuzumab. Of note the APT trial that backs this up and included patients with tumors up to 3cm-T2 lesions.

Question 13

What is the treatment that is indicated for HER2+ disease that has not achieved a pCR? What if the patient doesn’t tolerate TDM-1?

Answer 13

TDM-1 is indicated for 14 cycles. If TDM-1 is stopped due to side effects put them on Trastuzumab +/- Pertuzumab. NCCN says if the patient was node positive and you give Trastuzumab you need to add Pertuzumab.

Question 14

What additional therapy can be offered to patients in early stage cancer, particularly postmenopausal patients to decrease the risk of distant recurrence in addition to endocrine/HER2/chemo?

Answer 14

Bisphosphonates or Xgeva which helps in both naturally and induced postmenopausal patients, NCCN says to give for 3-5 years. Per ASCO question: Zoledronic Acid is the only one that is assoc with a survival benefit (also decreases risk of bone mets). Xgeva also decreases risk of bone mets.

Question 15

What are the indications for adjuvant Abemaciclib in HR+ early stage disease in high risk patients?

Answer 15

So you give it to patients who have: 4 or more positive lymph nodes, 1-3 lymph nodes with either grade 3 disease OR tumor size of 5cm or more. Per ASCO, also use for Ki67 of 20 or higher

Question 16

What is the indication for adjuvant Olaparib in TNBC patients?

Answer 16

Residual disease after preoperative chemotherapy or pT2 or higher or pN1 or higher after adjuvant chemotherapy in those with a BRCA mutation.

Question 17

What is the indication for adjuvant Olaparib for HR+ disease?

Answer 17

For patients who have 4 or more positive lymph nodes after adjuvant chemo (cat 2 rec) or for those patients with residual disease after preoperative therapy and a CPS+EG score of 3 or higher

Question 18

What are the indications to give the Keynote-522 regimen in TNBC?

Answer 18

Stage II: T1 w/N1 or N2
Stage III: T2-T4 w/ N0-N2

T1-lesion up to 2 cm
T2-lesion from 2cm to 5 cm
Any lymph node positive disease is Stage II

Question 19

What is the follow up for a patient with early stage breast cancer?

Answer 19

1-4 times a year for the first 5 years and then yearly afterwards. Mammogram should be done yearly.

Question 20

What is the first line tx option for HER2+ metastatic/unresectable disease?

Answer 20

Pertuzumab, Trastuzumab with Docetaxel or you can do Paclitaxel

Question 21

What is the 2nd line option for HER2+ metastatic disease? What is the survival benefit seen with this drug?

Answer 21

Trastuzumab deruxtecan. There is a huge PFS benefit, for the OS the median hasn’t been reached.

Question 22

What is the 3rd line option for HER2+ metastatic disease? What is the survival benefit with the more specific HER2 drug?

Answer 22

Tucatinib, trastuzumab, capecitabine (preferred option). You can also do TDM1. Tucatinib is assoc with a PFS and OS benefit and CNS benefit!

Question 23

What are some common side effects of Trastuzumab Deruxtecan?

Answer 23

Interstitial lung disease, pneumonia/pneumonitis, all 3 cell lines can decrease, LFT increase, rash, joint pain, GI, alopecia

Question 24

What are the side effects of Tucatinib?

Answer 24

Diarrhea, stomatitis, hand/foot syndrome, nausea, LFT increase

Question 25

What are some fourth line options for HER2+ metastatic disease?

Answer 25

Capecitabine with trastuzumab or lapatinib, trastuzumab with paclitaxel +/- Carboplatin, Trastuzumab w/Docetaxel or Vinorelbine, Margetuximab plus chemo (capecitabine, eribulin, vinorelbine, gemcitabine).

Question 26

Which two CDK 4/6 inhibitors cause more myelosuppression?

Answer 26

Palbociclib and Ribociclib cause more immunosuppression while abemaciclib causes less of this.

Question 27

What are the side effects seen with Ribociclib?

Answer 27

In addition to cytopenias, LFTs, prolonged QTC, nausea, alopecia. While on this med you will need to monitor CBC, LFT, EKG

Question 28

What are some of the side effects seen with Abemaciclib?

Answer 28

Neutropenia, LFT increase, diarrhea, interstitial lung disease, AKI, VTE, cardiac arrest, CHF, Vfib. You have to check CBC and LFTs while on this med.

Question 29

What are the side effects seen with Palbociclib?

Answer 29

Myelosuppression (notorious for this), interstitial lung dx, hand foot syndrome, asthenia, GI, stomatitis, rash, blurry vision.

Question 30

What are your first line options for HR+ metastatic disease?

Answer 30

AI w/ CDK 4/6 inhibitor: Category 1 rec is Ribociclib due to OS benefit. Other option: Fulvestrant w/ CDK 4/6 inhibitor, with this Cat 1 Recs are Ribociclib and Abemaciclib. Abemaciclib thus far is trending towards an OS benefit. Palbociclib has not shown a OS benefit.

Question 31

What is the mechanism of action with a Fulvestrant?

Answer 31

It is a SERD so it binds to estrogen receptor and downregulates the ER receptor internally

Question 32

What are the 2nd line options for HR+ metastatic disease?

Answer 32

If they have a PIK3CA mutation you can use Alpelisib w/ Fulvestrant. Or if they have a PIK3CA, AKT1, or PTEN you use Capivasertib w/Fulvestrant. Everolimus w/exemestane, fulvestrant, or tamoxifen

Question 33

What is the mechanism of action with Capivasertib?

Answer 33

So it is a AKT inhibitor (inhibits AKT 1, 2, 3).

Question 34

What are the most important side effects seen with Alpelisib?

Answer 34

Hyperglycemia, skin rash, interstitial lung dx, uveitis, osteonecrosis of the jaw, and diarrhea. Can increase aPTT, lipase, GGT.

Question 35

What are some of the side effects seen with Capivasertib?

Answer 35

Hyperglycemia, ketoacidosis, diarrhea, skin rash, hand/foot dx, AKI, GI, neutropenia/lymphopenia

Question 36

When a patient was on a AI for early stage dx and has a metastatic recurrence within 12 months what is the best next step?

Answer 36

If they last had a dose of a AI within 12 months they are considered endocrine resistant. So for these patients you need to give them Fulvestrant + CDK 4/6

Question 37

What medication is approved for a ESR1 mutation in the second line and beyond setting?

Answer 37

Elascestrant

Question 38

What is the first line tx option for TNBC metastatic dx? What is the survival benefit?

Answer 38

So all patients need their CPS checked. If it’s 10 or higher you give Pembro w/ Nab-paclitaxel or Carbo w/ Gemcitabine. Adding Pembro is assoc with a OS benefit. If less than 10 you give chemo alone.

Question 39

How do you approach a patient who has a visceral crisis with either HR+ or HR- disease and HER2-?

Answer 39

In general you want to use a two drug regimen such as Carboplatin/Paclitaxel, Gemcitabine/Carboplatin, Gemcitabine/Paclitaxel, Doxorubincin/Cyclophosphamide

Question 40

For metastatic TNBC that also has a BRCA 1/2 mutation and CPS less than 10 how do you treat these patients? What if a patient has both a BRCA 1/2 mutation and a CPS>10?

Answer 40

Olaparib, talazoparib or you could use a platinum agent cisplatin or carboplatin. Both are Cat 1 rec preferred options, but these are options only if the CPS is less than 10. Remember if a patient has BRCA 1/2 and CPS of 10 or higher choose immunotherapy w/chemo.

Question 41

What are the second line options for TNBC?

Answer 41

So if they have a BRCA mutation you give Olaparib or Talazoparib. If they have a HER2 1+ or HER2 2+ w/FISH neg you give Trastuzumab Deruxtecan. The other option is Sacituzumab. Both Sacituzumab and Trastuzumab are Cat 1 recs. Single agent chemo is another option, but not preferred.

Question 42

What kind of drug is Sacituzumab and what chemo agent is it linked to and what antigen on the cell surface does it recognize?

Answer 42

It is a antibody/drug conjugate. The chemo is SN-38 which is a topoisomerase I inhibitor. It recognizes the Trop-2 antigen.

Question 43

What is the survival benefit of Sacitzumab in the third line and beyond setting?

Answer 43

It has a OS benefit of 5.4 months (this was based off a slide done at GW presentation last year).

Question 44

What is the survival benefit with PARP-i in metastatic disease?

Answer 44

Both inhibitors are only assoc with a PFS benefit and not a OS benefit. She said in the slide that Olaparib may be assoc with a OS benefit in a specific subset of patients.

Question 45

What are the first line options for HR+ metastatic disease that is endocrine refractory?

Answer 45

For those that are BRCA 1/2 + you give PARP-i, if they are negative for this you give traditional chemo.

Question 46

What are the 2nd line options for HR+ metastatic breast cancer?

Answer 46

Sacituzumab Govitecan or if they are HER2 1+ or HER2 2+ with FISH neg you give Traztuzumab Deruxtecan. These are both Cat 1 recs. Chemo is your other option.

Question 47

Your traditional targeted therapy for metastatic HR+ and HR- breast cancer is used in what setting?

Answer 47

Second line
Examples: NTRK (Larotrectinib), RET (Selpercatinib), MSI-H, ddMMR
The guidelines say only if there are no satisfactory first line options can you use these options in the first line setting.

Question 48

What is the cutoff when deciding to give neoadjuvant chemo for TNBC as opposed to adjuvant chemo?

Answer 48

The tumor must be 2cm or larger and/or lymph node positive. It is indicated for Stage II and III dx.

Question 49

When can chemo be safely given in pregnancy?

Answer 49

So the ASCO question said this can be done safely in the second and third trimester, the question said AC can be given in the second while paclitaxel can safely be added in the third trimester.

Question 50

What is the best next step in early stage HER2+ that did not achieve a pCR? What if they can’t tolerate this drug?

Answer 50

TDM1 is the best next step. If they didn’t tolerate it, then you give Trastuzumab +|- Pertuzumab.

Question 51

When patients undergo preoperative therapy or do not receive but after surgery have a pCR for HER2+ disease what is the best next step?

Answer 51

Trastuzumab +/- Pertuzumab for a year

Question 52

For those patients who have both HER2+ and HR+ early stage breast cancer and are perceived at high risk of recurrence, what tx can you do after they complete HER2+ adjuvant tx?

Answer 52

You can give extended use of Neratinib but this must be weighed against the risk of toxicity. It hasn’t been studied in patients who received Pertuzumab and TDM1.

Question 53

What is the resection margin for DCIS and invasive carcinoma?

Answer 53

DCIS-2mm
Invasive dx-no ink on tumor

Question 54

In males which BRCA gene carries the highest risk of breast cancer? In women, which BRCA gene carries the highest risk of breast cancer? Which one carries the highest risk for ovarian cancer?

Answer 54

Men-BRCA 2
Women-BRCA 1
Ovarian-BRCA 1

Question 55

For patient how have received prior thoracic RT, what are the screening guidelines for these patients? Relatives of BRCA patients?

Answer 55

Screening should start 8 years after RT and should also include a breast MRI. First degree relatives with BRCA mutation-these patients should have breast MRI added to mammogram.