#426 Breast Cancer for the PCP With Dr Sandhya Pruthi

February 12, 2024 | By Molly Heublein

Audio

Video

Transcript available via YouTube

Join us as Sandhya Pruthi, MD talks us through basics of breast cancer, specifically how to share a new diagnosis with a patient, the spectrum of disease from favorable to more aggressive, and the basics of what to expect with initial treatment. Feel more confident sharing a new diagnosis of breast cancer and supporting your patients through this journey.

Claim CME for this episode at curbsiders.vcuhealth.org!

Patreon | Episodes | Subscribe | Spotify | YouTube | Newsletter | Contact | Swag! | CME

Show Segments

00:00 Introduction

02:18 Getting to Know Dr Sandhya Pruthi

09:49 Picks of the Week

12:35 Case 1: Diagnosis and Treatment of ductal carcinoma in situ (DCIS)

21:24 Risk Stratification and Active Surveillance for DCIS

23:43 Genetic Testing Recommendations

28:08 Case 2: Evaluation and Diagnosis of a Breast Lump

39:14 Invasive Ductal Carcinoma

47:49 Initial Management of invasive ductal carcinoma (IDC)

48:19 Preoperative Discussion and MRI

49:19 Lumpectomy and Sentinel Lymph Node Biopsy

50:16 Radiation and Hormonal Adjuvant Therapy

51:46 Considerations for Chemotherapy

55:51 Signs of Late Recurrence or Metastasis

58:20 Screening Guidelines and Age

01:02:25 Importance of Breast Self-Awareness

Breast Cancer for the PCP- Pearls

1. Breast cancer is a heterogeneous disease. Understanding breast cancer biology gives insight into the potential treatments and prognosis.
2. Low risk to high risk breast conditions exist across a spectrum. Benign fibrocystic changes—> atypia—> DCIS (grade 1, 2, and 3) —> Invasive Cancer (hormone receptor positive more favorable than estrogen/progesterone receptor (ER/PR) negative, HER2 negative more favorable than HER2+, low Ki67 proliferation score more favorable than high Ki67 score; etc)
3. Education is key! Helping patients anticipate possible outcomes of biopsies helps prepare them for receiving results. Patients who understand the basics of their breast cancer biology can make more informed treatment decisions. 
4. Current recommendations for treatment of ductal carcinoma in situ (DCIS) include lumpectomy +/- radiation therapy vs mastectomy. Patients may also be treated with anti-estrogen medications.
5. Ongoing research is helping identify cases of DCIS that are less likely to progress to invasive ductal carcinoma (IDC) and allow deescalation of treatment or options for active surveillance. 
6. Invasive ductal carcinoma is similarly heterogenous, and treatment should be tailored to the individual patient based on their cancer biology.
7. PCPs should be aware of the risk of late recurrence of IDC, especially hormone receptor positive cancers, which can manifest decades later.

Breast Cancer Biology: the 101

Breast cancer is a heterogeneous disease. Understanding breast cancer biology gives insight into the potential treatments and prognosis.

Ductal Carcinoma in Situ (DCIS)

DCIS has a very favorable prognosis. Dr Pruthi describes DCIS as a “contained cancer” within the glands or milk ducts of the breast. At this stage, it does not have an opportunity to spread. DCIS is typically diagnosed after mammographic findings of asymptomatic calcifications. It is somewhat controversial if DCIS is considered a “precancer” vs a “contained cancer”. There is a risk that DCIS can transition into invasive cancer, but it is a heterogeneous disease and not all will progress (Grimm 2022). About 50,000 patients in the US will be diagnosed with DCIS– much lower numbers than the more than 200,000 who are diagnosed with invasive ductal carcinoma (IDC) (ACS 2024).

Patient Communication around a new Cancer Diagnosis 

Dr Pruthi recommends pre-education for patients going in for a breast biopsy. Prepare patients that biopsy results of mammographic calcifications can span a spectrum from benign fibrocystic changes to atypia to DCIS. This prep work will make the discussion about the results much easier. 

With a new cancer diagnosis, Dr Pruthi highlights that it is ideal to share this news in person, but sometimes that’s not feasible. When she calls a patient with a new diagnosis of DCIS, she makes sure to stress that there is no role for chemotherapy in treatment of DCIS. 

DCIS Treatment

Standard Treatment

Surgical removal of DCIS is currently standard of care– the size of the DCIS and patient preferences help decide if lumpectomy or mastectomy is preferred. In patients with lumpectomy, radiation is typically suggested, as radiation + lumpectomy is considered to confer equal risk of local cancer recurrence as mastectomy. In some patients at low risk and at older age, radiation is not needed even after lumpectomy (Peppercorn 2017, Farante 2022). Some patients may benefit from oral hormonal blockers such as tamoxifen or aromatase inhibitors for estrogen receptor (ER) positive cases (Hwang 2020).

Active Surveillance

As there is an appreciation that some cases of DCIS will not progress to invasive cancer, there is growing work to determine when deescalation of treatment is appropriate. The COMET trial is looking at women with low to intermediate risk DCIS. The study compared active surveillance (every 6 month mammograms for 5 years) vs typical treatment (surgery +/- radiation). Either arm could be treated with anti-estrogen medications. In the active surveillance arm, if the calcifications increased in size past 5mm, they were rebiopsied. Dr Pruthi is hoping we will see full analysis and trial publication in the next year, but anecdotally she has seen some patients not progress with active surveillance and do well with limited treatment (expert opinion). 

Genetic Testing for Breast Cancer

Per American Cancer Society (ACS) recommendations, patients diagnosed with breast cancer (DCIS or invasive) under the age of 60 should be offered to meet with a genetic counselor to consider genetic testing (Desai 2020). Dr Pruthi highlights that genetic testing is much less expensive than it used to be (now around $250) and can test multiple genes as compared to older panels. Since our recording, a new guideline from ASCO- Society of Surgical Oncology suggested extending germline mutation testing to all patients diagnosed with breast cancer under the age of 65 (Bedrosian 2024).

Any woman with a strong family history of breast cancer (>1 family member with breast cancer before age 50, or ovarian cancer, male with breast cancer, family member with both breast and ovarian cancer) should be considered for genetic testing. Ideally the person with cancer should be tested before family members, but if this is not possible, it is reasonable to refer your patient with a positive family history to a genetics counselor (NCCN 2020).

Testing can look for a large panel of genes, beyond just BRCA mutations. CHEK2, PALB2, ATM are moderate penetrance genes that significantly increase the risk of breast cancer, though less than BRCA mutations. Genetic testing from more than 5 years ago may have had more limited panels, so patients that were tested some time ago may be recommended to retest a more expanded panel (Graffeo 2022).

Evaluating a Breast Lump

Concerning lumps are firm, fixed, large, and/or associated with skin changes. The first step to evaluating a palpable breast lump is a bilateral diagnostic mammogram +/- focused ultrasound. Dr Pruthi highlights that it is not appropriate to order a routine screening mammogram for patients who are overdue for screening if they have a new breast complaint– the patient requires diagnostic imaging so that the radiologist is alerted to the concern in question. In rare cases, imaging (diagnostic mammogram and ultrasound) can provide a false negative. If you have a high risk patient/lump and the imaging is negative, you should pursue a tissue diagnosis, so it is important to have a patient follow up after imaging to discuss next steps. Dr Pruthi highlights cases of invasive lobular carcinoma that have been missed on imaging. 

Dr Pruthi does not recommend a breast MRI to evaluate a high risk breast lump that has negative mammogram/ultrasound. Breast MRIs are expensive and with a high risk lump you still need a tissue diagnosis (even if MRI is negative).

Invasive Breast Cancer

Invasive ductal (IDC) and lobular are most common. Mucinous, anaplastic, metaplastic are rare, more aggressive invasive types of breast cancer.

Understanding the biology of the specific patient’s breast cancer helps to guide treatment recommendations. Hormone markers (estrogen, progesterone) and HER2 sensitivity are essential as ER/PR+ cancers can be treated with oral hormone blockers and HER2+ cancers have specific anti-HER2 therapies. Ki67 is a proliferative marker which is tested on hormone positive tumors– high proliferation suggests more aggressive cancer so helps with risk stratification (Kreipe 2022). Oncotype DX or MammaPrint are multigene panels that can further risk stratify patients to suggest how aggressive treatment should be (Xin 2017)

In some cases an MRI pre-operatively can be helpful for surgical planning to assess the extent of disease, Dr Pruthi suggests. The downside to getting a breast MRI is the high false positive rate, this could lead to additional biopsies or potentially over treatment. Dr Pruthi’s expert opinion is that these are most helpful in patients with denser breasts (in whom size of tumor is harder to estimate on mammogram) and patients who are leaning more toward lumpectomy (instead of mastectomy).

IDC Treatment

After diagnosis of IDC, patients may undergo a range of treatments based on their cancer biology.

In less common situations, neoadjuvant therapy can be suggested for locally advanced cancers, triple negative (ER/PR-/HER2-) IDC, or cancers with other high risk features. Treating with chemotherapy and/or anti-HER2 immunotherapy (like trastuzumab) before surgery can help expand surgical options by shrinking the tumor early (Barchiesi 2020).

For lower risk tumors, surgery is the first step in treatment. When patients undergo surgery to remove the cancer (lumpectomy or mastectomy), Dr Pruthi says lymph node evaluation for metastasis is institution dependent. Axillary lymph node ultrasound with fine needle aspiration (FNA) if there is lymphadenopathy is offered at some sites, in contrast to more standard sentinel lymph node biopsy at time of lumpectomy/mastectomy. Most patients treated with lumpectomy will then be recommended to have radiation, while patients undergoing mastectomy typically are not treated with radiation therapy. In patients receiving radiation therapy, standard of care is typically hypofraction, or a shortened radiation schedule of 3 weeks of treatment with a boost (Gupta 2018). 

Patients who are ER/PR+ benefit from hormonal blockade with oral anti-estrogen medications. Tamoxifen (a selective estrogen receptor modulator or SERM) or aromatase inhibitors (AIs, ie exemestane, anastrozole, letrozole) for 5-10 years is recommended depending on the individual patient and on the breast cancer biology. Premenopausal patients should receive tamoxifen (unless they are undergoing ovarian suppression, in which case they could receive an AI), while postmenopausal patients can be treated with either AIs or tamoxifen. Considerations around the side effects of tamoxifen as compared to AIs factor into the choice of which agents to use. AIs are linked with worsening osteoporosis, while tamoxifen is linked with increased risk of endometrial/uterine cancer and increased blood clotting. Both are associated with vasomotor symptoms of menopause (Trayes 2021). Dr Pruthi recommends PCPs order a baseline DEXA on patients who are likely going to need to start an estrogen blocker, as this can help with planning.

Most cases of IDC do not benefit from chemotherapy. A higher risk tumor, ie a triple negative cancer, one with positive lymph nodes, and possibly higher oncotype may benefit from chemotherapy. 

Later Recurrence of Metastatic Breast Cancer

It is important for PCPs to be aware that breast cancer can metastasize many years after initial diagnosis. In ER/PR+ IDC metastases later than 5 years out from initial treatment (and up to decades later) are not rare. Most common sites for metastases are bone, brain, liver, and lungs. If a breast cancer survivor has developed new persistent symptoms, get imaging to rule out late recurrence. If there are findings on imaging concerning for metastasis, the area should be biopsied if possible for a tissue diagnosis, as sometimes the cancer biology can change over time (ie the cancer can develop HER2 positivity or lose estrogen sensitivity). Targeted treatments, including CDK 4/6 inhibitors, have significantly improved outcomes (Richman 2019). Patients can have controlled disease or even a cure after a metastasis.  (Please note, in the audio, our guest misspoke and said CDK1 inhibitor; the targeted treatment is CDK 4/6 inhibitors.)

Screening Mammograms

Dr Pruthi appreciates the differences in various breast cancer screening guidelines and recommends PCPs be aware of these different guidelines. Her personal recommendation is that all age eligible patients, especially those with dense breasts, screen with yearly mammograms.

USPSTF is in a comment phase (as of 2/2024) regarding lowering the age of initiating mammograms to age 40 (from age 50). The current guidelines from 2016 recommend biannual mammogram for women aged 50-74. Women aged 40-49 should consider personal preferences when screening.

American Cancer Society (ACS) 2015 guidelines recommend women age 45-55 receive yearly mammograms, women age 40-45 may choose to start mammography for screening, and women over age 55 should have a mammogram every 2 years (with the option of yearly) until they have significant comorbidities/life expectancy less than 10 years.

National Comprehensive Cancer Network (NCCN) 2023 guidelines recommend annual mammograms for average risk women age 40 and over.

Dr Pruthi recommends the importance of breast self awareness. If the patient feels something different in their breast, even if the mammogram is normal, they should come in for an exam with their PCP. 

When to Stop Screening Mammograms

Dr Pruthi suggests that in patients who are healthy and can make informed decisions at age 74 with a life expectancy >5-10 years it’s reasonable to continue screening (even though USPSTF guidelines only recommend up until age 74). In patients with multimorbidity and low life expectancy, the risks of screening outweigh the benefits. 

Links

1. Era’s Pick of the Week: Renaissance, a film by Beyonce 
2. Molly’s Pick of the Week: Hudson Valley Seed Company Art Packs

Goal

Listeners will feel confident as the PCP supporting women with breast cancer.

Learning objectives

After listening to this episode listeners will…

1. Analyze the possible outcomes of breast biopsy and their implications.
2. Counsel patients on what to expect for next steps in treatment after new diagnosis of breast cancer.
3. Recognize common side effects of typical treatments for hormone receptor positive breast cancer.
4. Identify patterns of late recurrence of breast cancer.

Disclosures

Dr. Pruthi reports no relevant financial disclosures. The Curbsiders report no relevant financial disclosures. 

Citation

Heublein M, Pruthi S, Kryzhanovskaya E, Williams PN, Watto MF. “#426 Breast Cancer for the PCP”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast February 12, 2024.