Targeted therapy basics: HER2 treatment concepts and smart pre-visit questions

Some topics inch into my life sideways. A friend mentioned a new infusion on her calendar, and I realized I had a fuzzy grasp of how HER2-targeted therapy actually works in real life—what it is, when it’s used, and what I should ask if I were the one heading into a visit. I wanted a clear, calm map that balances what experts say with how it feels to prepare. This post is that map, written the way I’d explain it to a good friend who’s sorting through notes at the kitchen table.

The moment HER2 finally made sense to me

I kept hearing three short labels—HER2-positive, HER2-low, and HER2-negative—like train platforms. The big click was understanding they mainly describe how much of a growth-signal receptor (HER2) the tumor displays on its surface. That signal helps guide treatment choices. If a tumor is HER2-positive, therapies designed to lock onto HER2 are often front and center. If it’s HER2-low, a newer class (antibody–drug conjugates) may still help in some settings. If it’s HER2-negative, HER2-directed options typically aren’t used, and other targets or strategies take the lead.

  • High-value takeaway: your treatment options hinge on both biology (HER2, ER/PR, other biomarkers) and stage. Make sure your pathology report and any retesting are up to date.
  • Learn the exact words on your report (IHC 0, 1+, 2+ with ISH status, or 3+). This wording is how teams decide whether a drug fits your situation.
  • It’s normal to have gray zones and re-testing. Biology can vary between the original tumor and a later biopsy.

For a patient-friendly overview of how experts categorize HER2 and build treatment plans, I found the NCCN patient guideline especially helpful for translating terms into everyday language.

Meet the three main “families” of HER2-targeted treatment

It helped me to sort medicines by how they work rather than memorizing brand names:

  • Monoclonal antibodies (e.g., trastuzumab; often paired with pertuzumab). These are lab-made proteins that attach to HER2 on the tumor cell’s surface and block growth signals. In early-stage disease, they’re commonly paired with chemotherapy; in metastatic disease, they’re part of standard combinations.
  • Antibody–drug conjugates (ADCs) (e.g., ado-trastuzumab emtansine and fam-trastuzumab deruxtecan). Think of these as delivery trucks: the antibody finds HER2, and the attached chemotherapy payload is released near the tumor. Some ADCs can help even when the tumor shows lower levels of HER2. A practical must-know is that fam-trastuzumab deruxtecan has a boxed warning for interstitial lung disease/pneumonitis—teams watch closely for cough or shortness of breath; see the FDA labeling summary here.
  • Small-molecule tyrosine kinase inhibitors (TKIs) (e.g., tucatinib, lapatinib, neratinib). These are pills that block the HER2 signaling inside the cell. One important role: combinations that are designed to help when cancer has spread to the brain.

When I wanted the “no spin, just evidence” view, the NCI PDQ for clinicians gave me a sober summary of the data on combinations like trastuzumab–capecitabine–tucatinib (including outcomes for people with brain metastases).

How doctors tend to sequence these options

There isn’t one perfect path; it’s more like a set of well-traveled routes with forks based on stage, hormone receptor status, prior treatment, side effects, and personal preferences. Here’s the pattern I’ve seen described most often in plain English (your plan may differ):

  • Early-stage, HER2-positive: Many people receive a taxane chemotherapy plus trastuzumab (often with pertuzumab), followed by completion of about a year of anti-HER2 therapy. If residual disease remains after pre-surgery therapy, ado-trastuzumab emtansine may be used as a “cleanup” approach.
  • Metastatic, HER2-positive: A common first chapter includes trastuzumab + pertuzumab + chemotherapy. After that, ADCs—particularly fam-trastuzumab deruxtecan—often take center stage. For those with brain metastases or later lines, TKIs like tucatinib (with trastuzumab + capecitabine) are widely discussed because of brain activity.
  • HER2-low metastatic disease: Fam-trastuzumab deruxtecan has become an option for some people whose tumors show IHC 1+ or 2+/ISH-negative status after prior standard therapies.

If you like to skim a patient-friendly checklist of “what’s usually next if X happens,” the ASCO Cancer.Net page keeps a concise menu of HER2-directed options and where they tend to fit.

Safety first without the scare factor

Every therapy comes with trade-offs. I wanted to know the short list of side effects that deserve immediate attention, the ones that are common but manageable, and what monitoring looks like.

  • Heart monitoring with trastuzumab-based therapy: Because HER2 antibodies can affect heart function, teams often check an echocardiogram or MUGA scan on a schedule. Tell your team about any shortness of breath, swelling, or fatigue that feels different from your norm.
  • Lung risks with fam-trastuzumab deruxtecan: New or worsening cough, fever, or breathlessness can signal inflammation in the lungs (ILD/pneumonitis). Report these right away. Dose holds or steroids may be used if needed. (See the FDA label overview I linked above.)
  • TKI-related effects: Tucatinib and similar pills can cause diarrhea, skin changes, and effects on liver tests or creatinine (which can reflect kidney handling rather than true kidney damage). Teams are used to dose adjustments and supportive meds.
  • Infusion reactions: Chills, fever, or rash can happen with antibody infusions; premeds and slower rates are common solutions.
  • Fertility and pregnancy planning: HER2-directed drugs can pose fetal risks. Ask about contraception timing and the safest window for pregnancy discussions after treatment.

When I needed the “what exactly should I watch for” version, I bookmarked the FDA Enhertu label for lung-related warnings and my pharmacy’s handouts for practical day-to-day tips.

My two-minute framework for organizing a complex visit

I boiled my prep down to three steps that feel doable even on a distracted day:

  • Step 1—Notice: What has changed since last visit? Energy, breathing, cough, stools, rashes, headaches, vision changes, or memory fog?
  • Step 2—Compare: List your current regimen and timing (dose delays, missed pills, lab trends). Which side effects matter most to you this week?
  • Step 3—Confirm: Ask, “Given my HER2 status and prior treatments, is this still the best next step?” and “If we need to pivot, what would we pivot to and why?”

For evidence snapshots that clinicians use to weigh those pivots—including how tucatinib regimens performed in people with brain metastases—the NCI PDQ summary was the most balanced single page I found.

Real-life habits I’m trying to keep

I’m not perfect at any of these, but they’ve paid off:

  • One notebook, one app: I log infusion dates, pill times, side effects, and my “top three questions.” Even a few words a day helps me notice patterns.
  • Scheduled heart and lung check-ins: If I’m on a HER2 antibody or an ADC, I add reminders for echo scans or pulmonary symptom checklists so nothing slips.
  • Hydration and anti-diarrheal plan: With TKIs, I keep a written plan for what to take and when to call if diarrhea is more than I expected.
  • Vaccine timing: I ask about the best time around infusions or periods of low counts—sometimes shifting a vaccine by a week or two makes sense.
  • Contraception conversations: I keep this on the agenda even when it feels awkward; it matters for safety and planning.

Signals that tell me to slow down and call

I anchor on a few “yellow-to-red” flags. These don’t mean something terrible is happening; they mean it’s worth letting the team decide what’s next:

  • Breathing changes: New or worsening cough, fever, or shortness of breath—particularly relevant on fam-trastuzumab deruxtecan. Don’t wait around; message or call.
  • Heart-type symptoms: Unusual swelling, quick weight gain, chest discomfort, or suddenly limited exercise tolerance on trastuzumab-based therapy.
  • Neurologic shifts: Persistent headaches, new vision changes, or confusion—especially if brain metastases have ever been part of the conversation.
  • Uncontrolled diarrhea: If home meds aren’t touching it or you’re getting light-headed, that’s a same-day call.

If you prefer authoritative consumer language to check these against, the ASCO Cancer.Net treatment page is straightforward and updated regularly.

Smart pre-visit questions I wish I had earlier

Here’s the list I now keep on my phone. I pick 5–7 that fit the moment so the visit stays focused:

  • About the plan: “Where does this therapy fit in the usual sequence for my stage and HER2 status, and what would likely come next if we need to switch?”
  • About benefits: “What outcome are we aiming for right now—shrinking, stabilizing, delaying symptoms—and how will we measure that?”
  • About risks: “Which 2–3 side effects should I call you about immediately versus watch and wait?”
  • About life: “What routines (workouts, travel, vaccines, fertility plans) should I tweak during this treatment window?”
  • About tests: “Do I need a repeat biopsy or HER2 test if we’re considering an ADC for HER2-low disease?”
  • About the brain: “Given my situation, does it make sense to talk about regimens with activity in brain metastases?”
  • About monitoring: “How often will we check my heart or lungs, and what numbers on labs should I pay attention to?”
  • About alternatives: “If I don’t tolerate this dose, what are the usual dose-change steps before switching drugs?”
  • About trials: “Are there trials nearby that fit someone like me?” (Teams often search the NCI database in minutes.)

Quick links I kept open while learning

What I’m keeping and what I’m letting go

I’m keeping a bias for clarity: knowing my exact HER2 wording and asking for a one-sentence goal for each phase of therapy. I’m keeping the habit of naming my top two worries at the start of each visit (it steers the conversation so well). I’m letting go of the idea that there’s a single “best” plan for everyone with HER2-positive disease—there are patterns, but your biology, your prior therapies, and your life context matter. I’m also letting go of the fear that asking about side effects will “jinx” anything; it actually builds safety.

FAQ

1) Can HER2 status change over time?
Answer: It can. Tumors can evolve, and different sites may show different levels. That’s why teams sometimes recommend new testing if the plan might change, especially when considering an ADC for HER2-low disease (see the HER2 categories described in the NCCN patient guideline linked below).

2) If I’m HER2-positive and hormone-receptor-positive, which target comes first?
Answer: Both matter. In early-stage settings, anti-HER2 therapy with chemotherapy is common, followed by completion of a year of anti-HER2 therapy and appropriate endocrine therapy. In metastatic care, the mix depends on symptoms, sites of disease, and prior medicines; clinicians often consult frameworks like the NCI PDQ and NCCN recommendations.

3) Do any drugs work better for brain metastases?
Answer: Some regimens including tucatinib have shown activity in people with brain metastases. Your team will weigh systemic options alongside local approaches (radiation, surgery). The NCI PDQ page I linked summarizes data from the HER2CLIMB trial.

4) How serious is the lung risk with fam-trastuzumab deruxtecan?
Answer: The risk is real but manageable with close monitoring. The FDA label includes a boxed warning for interstitial lung disease/pneumonitis. Report cough, fever, or new shortness of breath promptly so your team can evaluate and adjust treatment if needed.

5) What if I’m HER2-low—do I still have “targeted” options?
Answer: In metastatic settings after certain prior therapies, fam-trastuzumab deruxtecan may be considered for HER2-low disease. Whether it fits depends on your prior treatments, overall health, and preferences. Ask your clinician to walk through where it would land in your sequence.

Sources & References

This blog is a personal journal and for general information only. It is not a substitute for professional medical advice, diagnosis, or treatment, and it does not create a doctor–patient relationship. Always seek the advice of a licensed clinician for questions about your health. If you may be experiencing an emergency, call your local emergency number immediately (e.g., 911 [US], 119).